CH623809A5 - Process for the preparation of pyrrolidones - Google Patents

Process for the preparation of pyrrolidones Download PDF

Info

Publication number: CH623809A5
Authority: CH; Switzerland
Prior art keywords: hexen; formula; ppm; carbon atoms; pyrrolidone
Prior art date: 1975-06-27

Application number

CH809976A

Other languages

German (de)

English (en)

Inventor

Wilhelm Dr Bartmann

Rudolf Dr Kunstmann

Ulrich Dr Lerch

Bernward Dr Schoelkens

Original Assignee

Hoechst Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1975-06-27

Filing date

1976-06-24

Publication date

1981-06-30

1976-06-24 Application filed by Hoechst Ag filed Critical Hoechst Ag

1981-06-30 Publication of CH623809A5 publication Critical patent/CH623809A5/de

Links

238000000034 method Methods 0.000 title claims description 20
238000002360 preparation method Methods 0.000 title claims description 10
150000004040 pyrrolidinones Chemical class 0.000 title claims description 4
-1 aliphatic hydrocarbon radical Chemical class 0.000 claims description 233
150000001875 compounds Chemical class 0.000 claims description 75
125000004432 carbon atom Chemical group C* 0.000 claims description 49
239000002253 acid Substances 0.000 claims description 32
150000007513 acids Chemical class 0.000 claims description 11
125000003545 alkoxy group Chemical group 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 9
229910052739 hydrogen Inorganic materials 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
KHUXNRRPPZOJPT-UHFFFAOYSA-N phenoxy radical Chemical compound O=C1C=C[CH]C=C1 KHUXNRRPPZOJPT-UHFFFAOYSA-N 0.000 claims description 8
239000004215 Carbon black (E152) Substances 0.000 claims description 6
229930195733 hydrocarbon Natural products 0.000 claims description 6
229910052751 metal Inorganic materials 0.000 claims description 6
239000002184 metal Substances 0.000 claims description 6
229920006395 saturated elastomer Polymers 0.000 claims description 6
229940094443 oxytocics prostaglandins Drugs 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
150000003180 prostaglandins Chemical class 0.000 claims description 5
125000003302 alkenyloxy group Chemical group 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
125000005297 thienyloxy group Chemical group S1C(=CC=C1)O* 0.000 claims description 4
125000001931 aliphatic group Chemical group 0.000 claims description 3
230000015572 biosynthetic process Effects 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 2
230000002829 reductive effect Effects 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
230000000144 pharmacologic effect Effects 0.000 claims 2
241000124008 Mammalia Species 0.000 claims 1
241001465754 Metazoa Species 0.000 claims 1
125000004185 ester group Chemical group 0.000 claims 1
229930014626 natural product Natural products 0.000 claims 1
230000001766 physiological effect Effects 0.000 claims 1
238000003786 synthesis reaction Methods 0.000 claims 1
230000001225 therapeutic effect Effects 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 90
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 60
238000004587 chromatography analysis Methods 0.000 description 49
238000006243 chemical reaction Methods 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
239000002904 solvent Substances 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
239000000203 mixture Substances 0.000 description 21
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 17
239000000243 solution Substances 0.000 description 17
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
239000002585 base Substances 0.000 description 16
239000000741 silica gel Substances 0.000 description 16
229910002027 silica gel Inorganic materials 0.000 description 16
150000002148 esters Chemical class 0.000 description 14
238000005804 alkylation reaction Methods 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
229960000583 acetic acid Drugs 0.000 description 12
230000029936 alkylation Effects 0.000 description 12
239000012362 glacial acetic acid Substances 0.000 description 12
150000002576 ketones Chemical class 0.000 description 11
229910052757 nitrogen Inorganic materials 0.000 description 10
125000006239 protecting group Chemical group 0.000 description 10
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
150000001450 anions Chemical class 0.000 description 8
150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
239000007795 chemical reaction product Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
125000003118 aryl group Chemical group 0.000 description 7
239000003480 eluent Substances 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
238000004140 cleaning Methods 0.000 description 6
230000032050 esterification Effects 0.000 description 6
238000005886 esterification reaction Methods 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
230000003647 oxidation Effects 0.000 description 6
238000007254 oxidation reaction Methods 0.000 description 6
238000005949 ozonolysis reaction Methods 0.000 description 6
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
238000001816 cooling Methods 0.000 description 5
150000002431 hydrogen Chemical group 0.000 description 5
150000003839 salts Chemical class 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
125000006241 alcohol protecting group Chemical group 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
230000033228 biological regulation Effects 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
238000011097 chromatography purification Methods 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
150000002170 ethers Chemical class 0.000 description 4
229910052731 fluorine Inorganic materials 0.000 description 4
239000011737 fluorine Substances 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
238000010992 reflux Methods 0.000 description 4
GJFVJZNQGLSMMQ-RQOWECAXSA-N (z)-7-bromohept-5-enoic acid Chemical compound OC(=O)CCC\C=C/CBr GJFVJZNQGLSMMQ-RQOWECAXSA-N 0.000 description 3
LQZCYXCHWNQBKX-UHFFFAOYSA-N 1-dimethoxyphosphorylheptan-2-one Chemical compound CCCCCC(=O)CP(=O)(OC)OC LQZCYXCHWNQBKX-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
238000006052 Horner reaction Methods 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
238000007239 Wittig reaction Methods 0.000 description 3
150000001338 aliphatic hydrocarbons Chemical group 0.000 description 3
150000001340 alkali metals Chemical group 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
239000012141 concentrate Substances 0.000 description 3
230000007717 exclusion Effects 0.000 description 3
150000008282 halocarbons Chemical class 0.000 description 3
230000001077 hypotensive effect Effects 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
OEWJGOMAYLEAKO-HYXAFXHYSA-N methyl (z)-7-bromohept-5-enoate Chemical compound COC(=O)CCC\C=C/CBr OEWJGOMAYLEAKO-HYXAFXHYSA-N 0.000 description 3
159000000000 sodium salts Chemical class 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
238000005292 vacuum distillation Methods 0.000 description 3
PJEXUIKBGBSHBS-UHFFFAOYSA-N 1-(hydroxymethyl)pyrrolidin-2-one Chemical compound OCN1CCCC1=O PJEXUIKBGBSHBS-UHFFFAOYSA-N 0.000 description 2
CKXKCMGANIESSL-UHFFFAOYSA-N 1-dimethoxyphosphoryl-4-ethoxy-3,3-dimethylbutan-2-one Chemical compound CCOCC(C)(C)C(=O)CP(=O)(OC)OC CKXKCMGANIESSL-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
HOBJEFOCIRXQKH-UHFFFAOYSA-N 5-(hydroxymethyl)pyrrolidin-2-one Chemical compound OCC1CCC(=O)N1 HOBJEFOCIRXQKH-UHFFFAOYSA-N 0.000 description 2
VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
208000001953 Hypotension Diseases 0.000 description 2
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 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
150000001336 alkenes Chemical class 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
229940124630 bronchodilator Drugs 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
150000001721 carbon Chemical group 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
239000012043 crude product Substances 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
238000001035 drying Methods 0.000 description 2
230000008030 elimination Effects 0.000 description 2
238000003379 elimination reaction Methods 0.000 description 2
FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 2
238000000605 extraction Methods 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
208000021822 hypotensive Diseases 0.000 description 2
239000011261 inert gas Substances 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000011707 mineral Chemical class 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
230000020477 pH reduction Effects 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 2
150000004714 phosphonium salts Chemical class 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
238000000746 purification Methods 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
PSOLOGTXFROOBF-UHFFFAOYSA-N (9-methyl-2-oxodecyl)phosphonic acid Chemical compound CC(C)CCCCCCC(=O)CP(O)(O)=O PSOLOGTXFROOBF-UHFFFAOYSA-N 0.000 description 1
WIYMDOCSCMPUJI-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3,3-dimethylheptan-2-one Chemical compound CCCCC(C)(C)C(=O)CP(=O)(OC)OC WIYMDOCSCMPUJI-UHFFFAOYSA-N 0.000 description 1
ONYIBVIIOCEBIV-UHFFFAOYSA-N 1-dimethoxyphosphoryl-4-phenylbutan-2-one Chemical compound COP(=O)(OC)CC(=O)CCC1=CC=CC=C1 ONYIBVIIOCEBIV-UHFFFAOYSA-N 0.000 description 1
OWTUAGFQGWALSI-UHFFFAOYSA-N 1-dimethoxyphosphoryl-6-methylheptan-2-one Chemical compound COP(=O)(OC)CC(=O)CCCC(C)C OWTUAGFQGWALSI-UHFFFAOYSA-N 0.000 description 1
ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 1
YOWQWFMSQCOSBA-UHFFFAOYSA-N 2-methoxypropene Chemical compound COC(C)=C YOWQWFMSQCOSBA-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000002516 radical scavenger Substances 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
239000002994 raw material Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
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MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
229910001925 ruthenium oxide Inorganic materials 0.000 description 1
WOCIAKWEIIZHES-UHFFFAOYSA-N ruthenium(iv) oxide Chemical compound O=[Ru]=O WOCIAKWEIIZHES-UHFFFAOYSA-N 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000028327 secretion Effects 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
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WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
229910000342 sodium bisulfate Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
JXHZRQHZVYDRGX-UHFFFAOYSA-M sodium;hydrogen sulfate;hydrate Chemical compound [OH-].[Na+].OS(O)(=O)=O JXHZRQHZVYDRGX-UHFFFAOYSA-M 0.000 description 1
238000007711 solidification Methods 0.000 description 1
230000008023 solidification Effects 0.000 description 1
230000003033 spasmogenic effect Effects 0.000 description 1
230000002048 spasmolytic effect Effects 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
150000005846 sugar alcohols Polymers 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
MDDUHVRJJAFRAU-YZNNVMRBSA-N tert-butyl-[(1r,3s,5z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-4-methylidenecyclohexyl]oxy-dimethylsilane Chemical compound C1[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)C(=C)\C1=C/CP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 MDDUHVRJJAFRAU-YZNNVMRBSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
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FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
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239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pyrrole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CH809976A 1975-06-27 1976-06-24 Process for the preparation of pyrrolidones CH623809A5 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19752528664 DE2528664A1 (de)	1975-06-27	1975-06-27	Pyrrolidone und verfahren zu ihrer herstellung

Publications (1)

Publication Number	Publication Date
CH623809A5 true CH623809A5 (en)	1981-06-30

Family

ID=5950059

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH809976A CH623809A5 (en)	1975-06-27	1976-06-24	Process for the preparation of pyrrolidones

Country Status (14)

Country	Link
JP (1)	JPS525764A (fr)
AT (1)	AT365575B (fr)
BE (1)	BE843505A (fr)
CH (1)	CH623809A5 (fr)
DE (1)	DE2528664A1 (fr)
DK (1)	DK287476A (fr)
ES (1)	ES449095A1 (fr)
FR (1)	FR2316943A1 (fr)
GB (1)	GB1553595A (fr)
IL (1)	IL49916A0 (fr)
LU (1)	LU75235A1 (fr)
NL (1)	NL7606773A (fr)
SE (1)	SE7607331L (fr)
ZA (1)	ZA763802B (fr)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE423813B (sv) *	1976-08-06	1982-06-07	Pfizer	Forfarande for framstellning av 1,5-disubstituerade pyrrolidoner med terapeutiska egenskaper
US4772601A (en) *	1988-01-25	1988-09-20	Hoechst-Roussel Pharmaceuticals, Inc.	5-Substituted 1-(4-(1-pyrrolidinyl)-2-butynyl)-2-pyrrolidinones, pharmaceutical compositions and use
PL356662A1 (en) *	1999-12-22	2004-06-28	Pfizer Products Inc.	Ep4 receptor selective agonists in the treatment of osteoporosis
AU2001290250A1 (en) *	2000-09-21	2002-04-02	Ono Pharmaceutical Co. Ltd.	Ep4 receptor agonists containing 8-azaprostaglandin derivatives as the active ingredient
NZ525164A (en)	2000-11-27	2005-04-29	Pfizer Prod Inc	EP4 receptor selective agonists in the treatment of osteoporosis
ES2254726T3 (es)	2001-07-16	2006-06-16	F. Hoffmann-La Roche Ag	Analogos de prostaglandina como agonistas receptores de ep4.
EP1408961B1 (fr)	2001-07-16	2007-07-11	F. Hoffmann-La Roche Ag	Derives de pyrrolidone comme antagonistes de prostanoide
CN101921220B (zh)	2001-07-23	2013-05-22	小野药品工业株式会社	治疗与骨质损失有关的疾病的含有ep4激动剂作为活性成分的药物组合物
WO2003077910A1 (fr) *	2002-03-18	2003-09-25	Pfizer Products Inc.	Procedes de traitement au moyen d'agonistes selectifs du recepteur ep4
US6573294B1 (en)	2002-05-14	2003-06-03	Allergan, Inc.	8-azaprostaglandin analogs as agents for lowering intraocular pressure
BRPI0406717A (pt)	2003-01-10	2005-12-20	Hoffmann La Roche	Composto, composição farmacêutica que compreende o mesmo, método de tratamento de uma enfermidade em um mamìfero, utilização do composto e processo para a sua produção
US7179820B2 (en)	2003-06-06	2007-02-20	Allergan, Inc.	Piperidinyl prostaglandin E analogs
HUE031885T2 (en)	2012-07-19	2017-08-28	Cayman Chemical Co Inc	Difluoro lactam preparations for EP4-mediated osteo-related diseases and conditions
ES2635635T3 (es)	2013-03-15	2017-10-04	Cayman Chemical Company, Incorporated	Compuestos de difluorolactama como agonistas selectivos del receptor EP4 para su uso en el tratamiento de enfermedades y afecciones mediadas por EP4
WO2014144500A2 (fr)	2013-03-15	2014-09-18	Cayman Chemical Company, Inc.	Procédés de synthèse d'un analogue difluorolactam
US9676712B2 (en)	2013-03-15	2017-06-13	Cayman Chemical Company, Inc.	Lactam compounds as EP4 receptor-selective agonists for use in the treatment of EP4-mediated diseases and conditions
KR20160048054A (ko)	2013-07-19	2016-05-03	카이맨 케미칼 컴파니 인코포레이티드	골 성장의 촉진을 위한 방법, 시스템 및 조성물

1975
- 1975-06-27 DE DE19752528664 patent/DE2528664A1/de not_active Withdrawn
1976
- 1976-06-22 ES ES449095A patent/ES449095A1/es not_active Expired
- 1976-06-22 NL NL7606773A patent/NL7606773A/xx not_active Application Discontinuation
- 1976-06-24 SE SE7607331A patent/SE7607331L/xx unknown
- 1976-06-24 LU LU75235A patent/LU75235A1/xx unknown
- 1976-06-24 CH CH809976A patent/CH623809A5/de not_active IP Right Cessation
- 1976-06-25 GB GB26564/76A patent/GB1553595A/en not_active Expired
- 1976-06-25 IL IL49916A patent/IL49916A0/xx unknown
- 1976-06-25 DK DK287476A patent/DK287476A/da unknown
- 1976-06-25 AT AT0467976A patent/AT365575B/de active
- 1976-06-25 ZA ZA763802A patent/ZA763802B/xx unknown
- 1976-06-26 JP JP51075954A patent/JPS525764A/ja active Pending
- 1976-06-28 BE BE168390A patent/BE843505A/fr not_active IP Right Cessation
- 1976-06-28 FR FR7619563A patent/FR2316943A1/fr active Granted

Also Published As

Publication number	Publication date
FR2316943A1 (fr)	1977-02-04
GB1553595A (en)	1979-09-26
JPS525764A (en)	1977-01-17
IL49916A0 (en)	1976-08-31
LU75235A1 (fr)	1977-03-16
FR2316943B1 (fr)	1978-11-03
AT365575B (de)	1982-01-25
BE843505A (fr)	1976-12-28
ES449095A1 (es)	1977-12-16
DK287476A (da)	1976-12-28
ZA763802B (en)	1977-05-25
DE2528664A1 (de)	1977-01-13
NL7606773A (nl)	1976-12-29
ATA467976A (de)	1981-06-15
SE7607331L (sv)	1976-12-28

Legal Events

Date	Code	Title	Description
1987-02-27	PL	Patent ceased
2024-10-31	PL	Patent ceased

Publication	Publication Date	Title
DE2528664A1 (de)	1977-01-13	Pyrrolidone und verfahren zu ihrer herstellung
DE2619638A1 (de)	1977-11-17	Pyrrolidone und verfahren zu ihrer herstellung
DE2355731C3 (de)	1981-01-15	Derivate von w -nor-Prostaglandinen- E2IUId -F2 a , Verfahren zu ihrer Herstellung sowie diese enthaltende pharmazeutische Zusammensetzungen Pfizer Ine, New York, N.Y. (YStA.)
DE2731868A1 (de)	1978-02-02	15-deoxy-16-hydroxy-16-substituierte- prostansaeuren, derivate hiervon und verfahren zu ihrer herstellung
CH645631A5 (en)	1984-10-15	Process for the preparation of hydantoin derivatives
EP0007490B1 (fr)	1982-02-24	Composés prostaglandines de type PGE delta-2,4-11-désoxy, procédé pour leur préparation et leur application thérapeutique
DE2422924A1 (de)	1975-11-27	Thiaprostaglandine
DE3141387A1 (de)	1982-08-12	6-substituierte 6h-dibenzo(b,d)pyran-derivate, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische mittel
DE2346706A1 (de)	1975-04-03	Neue, nicht natuerlich vorkommende analoga von prostansaeuren und verfahren zu ihrer herstellung
DD282016A5 (de)	1990-08-29	Verfahren zur herstellung neuer ungesaettigter aminosaeureverbindungen
DE2611788C2 (de)	1986-03-27	Fluorprostaglandine, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Mittel
DE2917456C2 (fr)	1991-01-10
US4079145A (en)	1978-03-14	Certain pyrrolidone derivatives and pharmaceutical use thereof
DE2452536A1 (de)	1976-05-13	Pyrrolidone und verfahren zu ihrer herstellung
DE3853126T2 (de)	1995-06-14	Derivate der fluorierten Arachidonsäure.
DE2550004A1 (de)	1977-05-18	Thiaprostaglandine
DE2825855A1 (de)	1978-12-14	15-substituierte- omega -pentanorprostaglandin-derivate
DE3541346A1 (de)	1986-05-28	Acylaminohydroxyalkanoylamino- und -iminosaeuren und -ester und ihre salze
EP0065200B1 (fr)	1987-02-25	Thiolactiméthers de delta 1-pyrrolidine et leur procédé de préparation
DE2559093C3 (de)	1981-12-24	2-Desarboxy-2-[tetrazol-5-yl]-11-desoxy-ω-pentanorprostaglandine der E- oder F-Reihe und deren C↓15↓-Epimere
EP0231744B1 (fr)	1990-05-30	Pyrrol-1-yl-phényl-dihydropyridazinones substituées, leur préparation et leur utilisation
DE2234706A1 (de)	1973-02-01	Derivate von 9-oxo-13-trans-prostensaeureestern
DE2701455A1 (de)	1977-07-21	Neue cyclopentanverbindungen
WO1995000522A1 (fr)	1995-01-05	Derives d'acide phosphosuccinique et leur utilisation comme medicaments
CH631441A5 (de)	1982-08-13	Verfahren zur herstellung neuer cyclopentanderivate.