DK162768B - Fremgangsmaade til fremstilling af oxazolinoazetidinylhydroxymethylbutensyrederivater - Google Patents
Fremgangsmaade til fremstilling af oxazolinoazetidinylhydroxymethylbutensyrederivater Download PDFInfo
- Publication number
- DK162768B DK162768B DK032390A DK32390A DK162768B DK 162768 B DK162768 B DK 162768B DK 032390 A DK032390 A DK 032390A DK 32390 A DK32390 A DK 32390A DK 162768 B DK162768 B DK 162768B
- Authority
- DK
- Denmark
- Prior art keywords
- process according
- alkyl
- reduction
- carried out
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 17
- BAOHMJZBCIUQEO-UHFFFAOYSA-N 2-(hydroxymethyl)but-2-enoic acid Chemical class CC=C(CO)C(O)=O BAOHMJZBCIUQEO-UHFFFAOYSA-N 0.000 title claims description 3
- -1 hydroperoxide anion Chemical class 0.000 claims description 28
- 239000003153 chemical reaction reagent Substances 0.000 claims description 14
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 10
- 230000003647 oxidation Effects 0.000 claims description 10
- 238000007254 oxidation reaction Methods 0.000 claims description 10
- 230000001590 oxidative effect Effects 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229910000085 borane Inorganic materials 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 150000002496 iodine Chemical class 0.000 claims description 2
- 150000004972 metal peroxides Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- 239000011574 phosphorus Substances 0.000 claims description 2
- 239000000049 pigment Substances 0.000 claims description 2
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 claims 1
- 150000002497 iodine compounds Chemical class 0.000 claims 1
- 229910052987 metal hydride Inorganic materials 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 150000002148 esters Chemical class 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 235000009518 sodium iodide Nutrition 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 229910004373 HOAc Inorganic materials 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 4
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 4
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 239000004287 Dehydroacetic acid Substances 0.000 description 2
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- WDECIBYCCFPHNR-UHFFFAOYSA-N chrysene Chemical compound C1=CC=CC2=CC=C3C4=CC=CC=C4C=CC3=C21 WDECIBYCCFPHNR-UHFFFAOYSA-N 0.000 description 2
- JEQRBTDTEKWZBW-UHFFFAOYSA-N dehydroacetic acid Chemical compound CC(=O)C1=C(O)OC(C)=CC1=O JEQRBTDTEKWZBW-UHFFFAOYSA-N 0.000 description 2
- 235000019258 dehydroacetic acid Nutrition 0.000 description 2
- 229940061632 dehydroacetic acid Drugs 0.000 description 2
- PGRHXDWITVMQBC-UHFFFAOYSA-N dehydroacetic acid Natural products CC(=O)C1C(=O)OC(C)=CC1=O PGRHXDWITVMQBC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 150000005826 halohydrocarbons Chemical class 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 231100000989 no adverse effect Toxicity 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- JHNRZXQVBKRYKN-VQHVLOKHSA-N (ne)-n-(1-phenylethylidene)hydroxylamine Chemical compound O\N=C(/C)C1=CC=CC=C1 JHNRZXQVBKRYKN-VQHVLOKHSA-N 0.000 description 1
- DXBHBZVCASKNBY-UHFFFAOYSA-N 1,2-Benz(a)anthracene Chemical compound C1=CC=C2C3=CC4=CC=CC=C4C=C3C=CC2=C1 DXBHBZVCASKNBY-UHFFFAOYSA-N 0.000 description 1
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- JCYPECIVGRXBMO-UHFFFAOYSA-N 4-(dimethylamino)azobenzene Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=CC=C1 JCYPECIVGRXBMO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- FMMWHPNWAFZXNH-UHFFFAOYSA-N Benz[a]pyrene Chemical compound C1=C2C3=CC=CC=C3C=C(C=C3)C2=C2C3=CC=CC2=C1 FMMWHPNWAFZXNH-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- RSPISYXLHRIGJD-UHFFFAOYSA-N OOOO Chemical compound OOOO RSPISYXLHRIGJD-UHFFFAOYSA-N 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- TVJORGWKNPGCDW-UHFFFAOYSA-N aminoboron Chemical compound N[B] TVJORGWKNPGCDW-UHFFFAOYSA-N 0.000 description 1
- 229940107816 ammonium iodide Drugs 0.000 description 1
- 150000007860 aryl ester derivatives Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229940046413 calcium iodide Drugs 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000006182 dimethyl benzyl group Chemical group 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 1
- YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-M hydroperoxide group Chemical group [O-]O MHAJPDPJQMAIIY-UHFFFAOYSA-M 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 239000004434 industrial solvent Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229960004592 isopropanol Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000006178 methyl benzyl group Chemical group 0.000 description 1
- CEQFOVLGLXCDCX-WUKNDPDISA-N methyl red Chemical compound C1=CC(N(C)C)=CC=C1\N=N\C1=CC=CC=C1C(O)=O CEQFOVLGLXCDCX-WUKNDPDISA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
i
DK 162768 B
Den foreliggende opfindelse angår en fremgangsmåde til oxidation af et oxazolinoazetidinylhalogenmethylbutensyre-derivat (I) til frembringelse af det tilsvarende oxazolinoazetidinylhydroxymethylbutensyre-deri-vat (II) i henhold til følgende reaktionsskema
5 R
)-i fa _v j-f fz
-NCHCCH2Hal 7 _ncHCC^OH
10 (i) Coor1 coor1 hvori R betegner en al kyl-, aralkyl- eller arylgruppe, R* betegner et hydrogenatom eller en carboxybeskyttende gruppe, og Hal betegner et halogenatom, hvilken fremgangsmåde er ejendommelig ved det i krav l's ken-15 detegnende del angivne.
Kendte rremgangsmåder til omdannelse af en halogenmethylforbindel se til en hydroxymethyl forbi ndel se benytter i almindelighed hydrolyse af den tilsvarende iodmethylforbindelse.
Det har nu vist sig, at denne omdannelse forløber mere økonomisk og 20 med højere udbytte ved oxygenering, og den foreliggende opfindelse er baseret på denne erkendelse. Der er endvidere blevet bekræftet, at denne reaktion forløber tilfredsstillende med et oxidationsmiddel, selv med fortyndet molekylær oxygen, f.eks. luft.
Det er kendt, at produkterne (II), der fås ved denne fremgangsmåde, 25 er værdifulde som mellemprodukter ved fremstilling af værdifulde materialer, f.eks. antibakterielle midler af oxacephemtype (se f.eks. M.
Yoshioka et al., Tetrahedron Letters, bind 21, pp. 351-354 (1980)).
Alkyl-, aralkyl- eller arylgruppen R har fortrinsvis 1-12 carbon-atomer og kan være substitueret med en gruppe, som ikke har nogen ugun-30 stig virkning under reaktionsbetingelserne ifølge opfindelsen, f.eks. Cj-Cj-alkyl, nitro, Cj-Cg-alkoxy, monocyklisk aryloxy, halogen eller lignende.
Halogenet Hal kan være chlor, brom eller fortrinsvis iod.
Den carboxybeskyttende gruppe kan være en esterdannende gruppe 35 til beskyttelse af carboxygruppen under reaktionsbetingelserne ifølge opfindelsen. Foretrukne R*-grupper er lette at fjerne uden ugunstig virkning på produktet (II) efter reaktionen ifølge opfindelsen, når dette ønskes.
DK 162768 B
2
Repræsentative R^-grupper indeholder 1-20 carbonatomer og er velkendte inden for kemien, der vedrører antibakterielle midler af /5-lac-tam-type, og de indbefatter grupper, som danner alkylestere, f.eks. t-butyl-, cyclopropyl methyl-, allyl- eller 2,2,2-trichlorethylestere; 5 aral kyl estere, f.eks. benzyl-, methyl benzyl -, dimethyl benzyl-, methoxy-benzyl-, ethoxybenzyl-, nitrobenzyl-, aminobenzyl-, diphenylmethyl-, phthalidyl - eller phenacylestere; aryl estere, f.eks. phenyl-, penta-chlorphenyl- eller indanylestere; estere med en N-hydroxyaminoforbindel-se, f.eks. en ester med acetoneoxim, acetophenonoxim, acetaldoxim, N-10 hydroxysuccinimid eller N-hydroxyphthalimid; eller de kan erstattes med en gruppe, som danner et syreanhydrid med carbonsyre eller en carboxylsyre eller en amidgruppe.
Disse R^-grupper kan yderligere være substitueret med en gruppe, som ikke har nogen ugunstig virkning på reaktionen ifølge opfindelsen, 15 og kan være sådanne, som er eksemplificeret ovenfor i relation til R-gruppen.
De ovenfor definerede udgangsforbindelser (I) er kendte eller analoge med forbindelser beskrevet i den citerede Yoshioka et al. publikation eller anden litteratur vedrørende /3-lactam kemi.
20 Som anført ovenfor vedrører opfindelsen erstatning af halogen med hydroxy under indvirkning af et oxidationsreagens. Reaktionsforløbene illustreres nedenfor ved reaktionsskemaet
R R
25 NsssJ^O
']-i' HH2 )-1* CH2
-NQHCCH^Hal -NChHc^OH
(i) COOR1 COOR1 30 Hydroperoxid\^ reduktion^^-^^
-{ CH \_/ CH
oc I II 2 + π 2
35 0^-N?HCCH200H 0J_NCHCCHO
(in) coor1 (IV) ^oor1 hvori R, R* og Hal har den ovenfor definerede betydning.
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3
Oxidationsreagenset er et, som er i stand til at danne en hydroper-oxidanion eller et radikal ved hjælp af varme eller bestråling. Det frembragte oxazoli noazeti di nylhydroperoxymethyl butensyrederi vat (III) eller oxazolinoazetidinylformylbutensyrederivat (IV) reduceres til frem-5 bringelse af hydroxymethylforbindelsen (II).
i) Oxidation
Oxidationsreagenset til hydroperoxidoxidationen kan være oxygen, fortyndet oxygen som luft, hydrogenperoxid, metal peroxid eller lignende.
10 Denne reaktion kan accelereres ved bestråling, f.eks. med en wol framlampe, halogenlampe, kviksølvlampe eller sollys. Denne fotoreaktion kan understøttes af en forbindelse, som kan anslås til en stabil tri-plet-tilstand, dvs. en fotosensibilisator, f.eks. iod, et flerkernet aromatisk carbonhydrid, f.eks. benzanthracen, benzpyren, chrysen eller 15 pyren, en keton, f.eks. cyclopentanon, cyclohexanon eller fluorenon, et pigment, f.eks. eosin, fluorescein, methylrødt eller methylgult, en anden forbindelse, f.eks. phenothiazin, eller en anden radikal fremkaldende metode.
Alternativt kan reaktionen accelereres ved opvarmning til en tempe-20 ratur mellem 30 og 70°C, specielt mellem 50 og 60°C, selv i mørke, fortrinsvis i nærværelse af acetone, methyl ethyl keton, acetonitril, N-me-thylpyrrolidon, hexamethylphosphortriamid, dimethyl formamid, ethylencar-bonat, diethylcarbonat eller ved hjælp af anden radikal fremkaldende metode, hvorpå der er nævnt eksempler i forbindelse med bestrålet hydro-25 peroxidoxidation.
Både oxidation med et peroxid i lys og i mørke udføres sædvanligvis ved en temperatur mellem 0 og 100°C i et tidsrum mellem 10 minutter og 20 minutter i et neutralt eller svagt basisk medium til opfangning af det dannede hydrogenhalogenid og under omrøring eller bobledannelse.
30 Reaktionen udføres i et inert industrielt opløsningsmiddel, f.eks.
et vand-, carbonhydrid-, halogencarbonhydrid-, keton-, ester-, amid- eller alkoholopløsningsmiddel eller en blanding af disse. For eksempel kan opløsningsmidlet være benzen, dichlormethan, chloroform, carbontetra-chlorid, acetone, methyl ethyl keton, methyl isobutylketon, cyclopentanon, 35 cyclohexanon, ethylacetat, ethylcarbonat, ethylencarbonat, N,N-dimethyl-formamid, hexamethylphosphortriamid, 1-ethylpyrrolidin-2-on, 1,3-dime-thylimidazolidin-2-on, acetonitril, benzonitril, dimethyl sul foxid, iso-propanol, ethanol, methanol, vand eller en blanding af disse.
DK 162768 B
4
Blandt disse foretrækkes især vand-, halogencarbonhydrid- og esteropløsningsmidler, f.eks. vand, ethylacetat, dichlormethan, chloroform eller carbontetrachlorid.
Når oxygen er oxidationsreagenset, er hovedproduktet et aldehyd 5 (IV). Når hydrogenperoxid er oxidationsreagenset, er hovedproduktet et hydroperoxid (III), og når oxygen er oxidationsreagenset i nærvær af en syre og natriumiodid, er et hydroperoxid (III) hovedproduktet, men det reduceres derefter ved reaktionen i henhold til punkt i i) nedenfor til frembringelse af en alkohol (II).
10 Produktet (III) eller (IV) kan isoleres og renses på konventionel måde, f.eks. ved ekstraktion, vask, tørring, kromatografi, krystallisation eller lignende, eller det kan underkastes reduktionen ii) i næste trin samtidigt i reaktionsblandingen eller successivt uden isolering.
15 ii) Reduktion
Produktet (III) eller (IV) kan reduceres til frembringelse af den ønskede hydroxyforbindelse (II).
Reduktionen udføres ved indvirkning af et reduktionsreagens, som er i stand til at producere en hydroxymethylforbindelse (II) ud fra en hy-20 droxyperoxymethylforbi ndel se (III) eller en aldehydforbindelse (IV) på konventionel måde.
Repræsentative reduktionsreagenser til dette formål er til reduktion af hydroxyperoxidet (III), f.eks. en trivalent phosphorforbindelse, f.eks. en phosphorsyrlingester, en trialkylphosphin eller triarylphos-25 phin (et tri-Cj-C^-alkylphosphit, en tri-C^-C^-alkylphosphin, tri-mono-cyklisk aryl-phosphin eller lignende) eller et iodsalt plus en syre, f.eks. natrium-, kalium-, calcium- eller ammoniumiodid plus en syre, fortrinsvis en carboxylsyre (eddikesyre, dehydroeddikesyre, propionsyre, oxalsyre, benzoesyre eller lignende), og til reduktion af et aldehyd 30 (IV), f.eks. et al kalimetalborhydrid, alkalimetalaluminiumhydrid, alkalimetal (mono- eller di-)alkoxyaluminiumhydrid, boran, alkylboran, aminoboran eller lignende.
Reduktionen kan sædvanligvis udføres ved en temperatur mellem -50°C og 100°C i et tidsrum mellem 10 minutter og 5 timer i et inert opløs-35 ningsmiddel udvalgt blandt dem, der er beskrevet for oxidationen i) ovenfor, om nødvendigt under omrøring eller under inert gas, f.eks. nitrogen eller damp af det anvendte opløsningsmiddel*.
Opfindelsen beskrives nærmere i det følgende ved eksempler. I ta-
DK 162768 B
5 bellerne anvendes følgende forkortelser:
Ac = acetyl BH = diphenylmethyl DHa = dehydroeddikesyre ækv. = ækvivalent 5 Et = ethyl m-CPBA = m-chlorperbenzoesyre
St = stuetemperatur Ph = phenyl THF = tetrahydrofuran temp = temperatur 10 Eksempel 1
X JL
,r \-CH, -> ·._/ CH
oS5J-NCHCCH^Hal -NCHC-R^ (L) COOR1 ^ COOR1
En opløsning af (2R)-2-[(lR,5S)-3-R-7-oxo-4-oxa-2,6-diazabicyclo-20 [3.2.0jhept-2-en-6-yl]-3-halogenmethyl-3-butensyre-R^-ester (1) og et yderligere reagens i et opløsningsmiddel omrøres under tilstedeværelse af en opløsning af oxidationsreagenset eller et boblende gasformigt oxidationsreagens og, hvis dette er foreskrevet, under bestråling med en højspændings-kviksølvlampe eller halogenlampe. Det organiske lag vaskes 25 med vandig natriumthiosul fat, vandig natriumhydrogencarbonat og vand, tørres og koncentreres til frembringelse af den tilsvarende (2R)-2-[(lR,5$)-3-R-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl]-3-R2-3-butensyre-R^-ester (2). De enkelte komponenter kan i givet fald adskilles ved sil icagelkromatografi.
30 Reaktionsbetingelserne er anført i tabel (Γ), og de fysiske konstanter for produkterne er anført i tabel (II).
Under tilstedeværelse af natriumiodid og syre reduceres produkterne samtidigt ved en reduktion ifølge tabel (II;, og det isolerede hovedpro- . 2 dukt er forbindelsen (2), hvori R er hydroxymethyl.
DK 162768 B
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DK 162768 B
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DK 162768 B
8
Eksempel 2
ΐ R
»J-o 5 )—i “s * V—/ f2
0=J-NtpHCR 0=J-NCHCCH OH
/,x COOR1 . inm,l2
(1) (2) COOR
R =-CH200H,-CH0 10 Til en opløsning af (2R)-2-[(lR,5S)-3-R-7-oxo-4-oxa-2,6-diazabicyc- 2 1 lo[3.2.0]hept-2-en-6-yl]-3-R -3-butensyre-R -ester (l) i et opløsningsmiddel sættes et reduktionsmiddel, og blandingen omrøres ved den anførte temperatur i det anførte tidsrum. Reaktionsblandingen vaskes med vandig natriumhydrogencarbonat og vand, tørres og koncentreres til fjernelse af 15 opløsningsmidlet. Remanensen krystalliseres, hvorved (2R)-2-[(lR,5S)-3-R-7-oxo-4-oxa-2,6-diazabi cyclo-[3.2.0]hept-2-en-6-yl ]-3-R2-3-butensyre-R*-ester fås.
Reaktionsbetingelserne er anført i tabel (III), og de fysiske konstanter er som følger: 20 R = phenyl, R2 = hydroxymethyl, R1 = diphenylmethyl: smp. 100-140°C.
R = p-tolyl, R2 = hydroxymethyl, R1 = diphenylmethyl: smp. 124-126°C.
R = benzyl, R2 = hydroxymethyl, R1 = t-butyl: smp. 85-87°C.
DK 162768B
9
TABEL III REDUKTION AF MELLEMPRODUKTER
Eks. o R1 OP^snings- Reduktions-Te^. Tid udbytte^ R2 R K middel reagens .
nr* _(vægtdele) (ækv.) ( c) (min; __
1 Ph BH THF+HOAc NaBH, -50 60 83 C(l) CHO
(12)(4) (5) 4
2 Ph BH Et0Ac-Ho0 NaBH, 0 60 ..-CHO
(45)(5)2 (3.2? 59 C(2):CH200H
P(0CH_)_ 0 120 (1-5)3 3
, , - CHO
3 CH^CxH, BH Et0Ac+H_0 NaI+DHA st 30 82 C(3kCH 00H
364 (90) 2 (3) (4) 2
4 Ph BH EtOAc PPh- st 30 72 CHjOOH
(13) (1.2)
5 CH-CrH, BH EtOAc NaI-HOAc st 30 82 CH200H
3 6 4 (54) (2.2)(4.9)
6 PhCH. t-C, Hn EtOAc NaI+DHA st 30 74 C(4) CH 00H
2 4 9 (18) (3.7)(3.5) 2
7 Ph BH Et0Ac+ NaI+DHA st 20 71 C(5) CH2 00H
(9) (9) (7-3)(5.7)
8 Ph BH EtOAc NaI+DHA st 30 76 C(6) CH„00H
(6c) (9.3)(5.6) 2
9 CH-C.H, BH EtOAc Nal+HOAc st 30 90 CH200H
364 (54) (2.7)(4.7)
10 Ph BH CH2C1o-H90 NaI+HOAc st 20 77 C(8) C^OOH
(30) (10) (9) (5.3) 35 Udbytter med tilføjelsen C repræsenterer udbytter, der er beregnet ud fra kontinuert udførelse af reaktionerne i tabel (Ij og (III) uden isolering af mellemprodukterne. Tallene i parentes viser . · eksempel numrene i tabel (I;.
m* · · ·
Claims (10)
1- CH I II ^ -NCHCCH20H , COOR1 10 (ΙΪ) hvori R betegner en al kyl-, aralkyl- eller arylgruppe, og R* betegner et hydrogenatom eller en carboxybeskyttende gruppe, KENDETEGNET ved, AT man oxiderer det tilsvarende oxazolinoazetidinylhalogenmethylbutensyrederi -vat med formel (I) . 15 ' / \-' CH i II ^ -NCHCCH^Ha 1 ?n 000R1 (I) hvori R og R* har den ovenfor anførte betydning, og Hal betegner et halogenatom, med et hydroperoxidanion- eller et radikal dannende reagens og reducerer de dannede produkter.
1. Fremgangsmåde til fremstilling af et oxazolinoazetidinylhydroxymethyl butensyrederi vat med formlen (II) R
2. Fremgangsmåde ifølge krav 1, KENDETEGNET ved, AT R betegner en al kyl-, aralkyl- eller arylgruppe med 1-12 carbonatomer, der eventuelt er substitueret med en gruppe i form af Cj-C^-alkyl, nitro, Cj-C3-alko-xy, monocyklisk aryloxy eller halogen.
3. Fremgangsmåde ifølge krav 1 eller 2, KENDETEGNET ved, AT Hal be-30 tegner chlor eller brom.
4. Fremgangsmåde ifølge et eller flere af de foregående krav, KENDETEGNET ved, AT R* betegner en al kyl-, aralkyl- eller arylester-dannende gruppe med 1-20 carbonatomer.
5. Fremgangsmåde ifølge et af de foregående krav, KENDETEGNET ved,
35 AT det hydroperoxidanion- eller det radikaldannende reagens er oxygen, hydrogenperoxid eller metal peroxid.
5 I x t
6. Fremgangsmåde ifølge et ellen flere af de foregående krav, KENDETEGNET ved, AT oxidationen accelereres ved bestråling med eller uden DK 162768 B tilstedeværelse af en iodforbindelse, flerkernet aromatisk carbonhydrid, keton, pigment eller anden radikal fremkaldende foranstaltning eller opvarmning i mørke.
7. Fremgangsmåde ifølge et eller flere af de foregående krav, KEN-5 DETEGNET ved, AT oxidationen udføres ved en temperatur mellem 0 og 100°C i et tidsrum mellem 10 min. og 20 timer.
8. Fremgangsmåde ifølge et eller flere af de foregående krav, KENDETEGNET ved, AT reduktionen udføres med en trivalent phosphorforbindel-se eller et iodsalt plus en syre.
9. Fremgangsmåde ifølge et eller flere af de foregående krav, KEN DETEGNET ved, AT reduktionen udføres med et alkalimetalborhydrid, alka-1imetalaluminiumhydrid, alkalimetal (mono- eller di-)alkoxyaluminiumhy-drid, boran eller hydroxycarbylboran.
10. Fremgangsmåde et eller flere af de foregående krav, KENDETEGNET 15 ved, AT reduktionen udføres ved en temperatur mellem -50°C og 100°C i et tidsrum mellem 10 min. og 5 timer under en inert gas. 20 25
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6940282 | 1982-04-23 | ||
| JP57069402A JPS58185588A (ja) | 1982-04-23 | 1982-04-23 | 空気酸化によるハロメチル化合物の酸化方法および酸化生成物 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK32390A DK32390A (da) | 1990-02-07 |
| DK32390D0 DK32390D0 (da) | 1990-02-07 |
| DK162768B true DK162768B (da) | 1991-12-09 |
| DK162768C DK162768C (da) | 1992-04-27 |
Family
ID=13401568
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK179183A DK159446C (da) | 1982-04-23 | 1983-04-22 | Fremgangsmaade til fremstilling af oxazolinoazetidinylhydroxymethylbutensyrederivater |
| DK032390A DK162768C (da) | 1982-04-23 | 1990-02-07 | Fremgangsmaade til fremstilling af oxazolinoazetidinylhydroxymethylbutensyrederivater |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK179183A DK159446C (da) | 1982-04-23 | 1983-04-22 | Fremgangsmaade til fremstilling af oxazolinoazetidinylhydroxymethylbutensyrederivater |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US4581173A (da) |
| EP (2) | EP0093907B1 (da) |
| JP (1) | JPS58185588A (da) |
| KR (1) | KR890000032B1 (da) |
| AU (1) | AU553611B2 (da) |
| CA (1) | CA1194878A (da) |
| DE (1) | DE3370334D1 (da) |
| DK (2) | DK159446C (da) |
| GB (1) | GB2120241B (da) |
| GR (1) | GR78513B (da) |
| HU (1) | HU193038B (da) |
| IE (1) | IE55307B1 (da) |
| IL (1) | IL68475A (da) |
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|---|---|---|---|---|
| US8067650B2 (en) | 2006-08-24 | 2011-11-29 | Honeywell International Inc. | Process for the production of HFO trans-1234ze from HFC-245fa |
| US7485760B2 (en) | 2006-08-24 | 2009-02-03 | Honeywell International Inc. | Integrated HFC trans-1234ze manufacture process |
| CN116496298A (zh) * | 2023-05-04 | 2023-07-28 | 深圳六合六医疗器械有限公司 | 一锅法制备氟氧头孢中间体的方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1090806A (en) * | 1977-01-10 | 1980-12-02 | Mitsuru Yoshioka | Oxazolines |
| GB1557552A (en) * | 1977-02-15 | 1979-12-12 | Shionogi & Co | 1 oxadethiacepham compounds |
-
1982
- 1982-04-23 JP JP57069402A patent/JPS58185588A/ja active Granted
-
1983
- 1983-04-07 US US06/482,974 patent/US4581173A/en not_active Expired - Lifetime
- 1983-04-12 GR GR71064A patent/GR78513B/el unknown
- 1983-04-14 KR KR1019830001558A patent/KR890000032B1/ko not_active Expired
- 1983-04-20 GB GB08310691A patent/GB2120241B/en not_active Expired
- 1983-04-20 EP EP83103863A patent/EP0093907B1/en not_active Expired
- 1983-04-20 EP EP85107298A patent/EP0180709B1/en not_active Expired
- 1983-04-20 DE DE8383103863T patent/DE3370334D1/de not_active Expired
- 1983-04-21 IE IE912/83A patent/IE55307B1/en not_active IP Right Cessation
- 1983-04-22 HU HU831405A patent/HU193038B/hu unknown
- 1983-04-22 AU AU13878/83A patent/AU553611B2/en not_active Expired
- 1983-04-22 DK DK179183A patent/DK159446C/da not_active IP Right Cessation
- 1983-04-22 IL IL68475A patent/IL68475A/xx not_active IP Right Cessation
- 1983-04-25 CA CA000426670A patent/CA1194878A/en not_active Expired
-
1990
- 1990-02-07 DK DK032390A patent/DK162768C/da not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| GB8310691D0 (en) | 1983-05-25 |
| EP0180709B1 (en) | 1989-02-22 |
| GB2120241A (en) | 1983-11-30 |
| JPS58185588A (ja) | 1983-10-29 |
| KR890000032B1 (ko) | 1989-03-06 |
| DK159446B (da) | 1990-10-15 |
| DK179183D0 (da) | 1983-04-22 |
| IE55307B1 (en) | 1990-08-01 |
| AU553611B2 (en) | 1986-07-24 |
| DK179183A (da) | 1983-10-24 |
| EP0093907A1 (en) | 1983-11-16 |
| DK32390A (da) | 1990-02-07 |
| CA1194878A (en) | 1985-10-08 |
| KR840004433A (ko) | 1984-10-15 |
| GB2120241B (en) | 1985-05-09 |
| EP0180709A1 (en) | 1986-05-14 |
| EP0093907B1 (en) | 1987-03-18 |
| DE3370334D1 (en) | 1987-04-23 |
| DK162768C (da) | 1992-04-27 |
| IL68475A0 (en) | 1983-07-31 |
| IE830912L (en) | 1983-10-23 |
| GR78513B (da) | 1984-09-27 |
| JPH0242835B2 (da) | 1990-09-26 |
| US4581173A (en) | 1986-04-08 |
| IL68475A (en) | 1987-01-30 |
| HU193038B (en) | 1987-08-28 |
| AU1387883A (en) | 1983-10-27 |
| DK159446C (da) | 1991-03-18 |
| DK32390D0 (da) | 1990-02-07 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUP | Patent expired |