IL100360A - HISTORY OF PYROLIDINONE USED AS SUBSTANCE (S) -Vinyl and Alanyl GABA - Google Patents

HISTORY OF PYROLIDINONE USED AS SUBSTANCE (S) -Vinyl and Alanyl GABA

Info

Publication number: IL100360A
Authority: IL; Israel
Prior art keywords: solution; mmol; nmr; chloride; added
Prior art date: 1990-12-17

Application number

IL10036091A

Other languages

English (en)

Hebrew (he)

Other versions

IL100360A0 (en

Original Assignee

Merrell Dow Pharma

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.)

1990-12-17

Filing date

1991-12-12

Publication date

1998-08-16

1991-12-12 Application filed by Merrell Dow Pharma filed Critical Merrell Dow Pharma

1992-09-06 Publication of IL100360A0 publication Critical patent/IL100360A0/xx

1998-08-16 Publication of IL100360A publication Critical patent/IL100360A/en

Links

150000004040 pyrrolidinones Chemical class 0.000 title claims description 5
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 title claims description 5
239000000543 intermediate Substances 0.000 title abstract description 3
238000004519 manufacturing process Methods 0.000 title description 2
229920002554 vinyl polymer Polymers 0.000 title description 2
125000005282 allenyl group Chemical group 0.000 title 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims abstract description 5
238000000034 method Methods 0.000 claims description 16
238000005917 acylation reaction Methods 0.000 claims description 14
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 7
150000001875 compounds Chemical class 0.000 claims description 6
230000003287 optical effect Effects 0.000 claims description 4
125000002573 ethenylidene group Chemical group [*]=C=C([H])[H] 0.000 claims description 2
-1 1,5-disubstituted-pyrrolidinone Chemical class 0.000 abstract description 18
OYVDXEVJHXWJAE-RXMQYKEDSA-N (5s)-5-ethenylpyrrolidin-2-one Chemical compound C=C[C@@H]1CCC(=O)N1 OYVDXEVJHXWJAE-RXMQYKEDSA-N 0.000 abstract description 10
229960003692 gamma aminobutyric acid Drugs 0.000 abstract description 7
230000015572 biosynthetic process Effects 0.000 abstract description 4
230000000707 stereoselective effect Effects 0.000 abstract 1
238000003786 synthesis reaction Methods 0.000 abstract 1
239000000243 solution Substances 0.000 description 104
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 102
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 71
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
229910001868 water Inorganic materials 0.000 description 37
239000011541 reaction mixture Substances 0.000 description 34
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
238000005481 NMR spectroscopy Methods 0.000 description 32
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
238000006243 chemical reaction Methods 0.000 description 32
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 30
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 29
239000000741 silica gel Substances 0.000 description 29
229910002027 silica gel Inorganic materials 0.000 description 29
238000006460 hydrolysis reaction Methods 0.000 description 26
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
235000019439 ethyl acetate Nutrition 0.000 description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
230000007062 hydrolysis Effects 0.000 description 23
238000003756 stirring Methods 0.000 description 23
150000001450 anions Chemical class 0.000 description 21
238000000746 purification Methods 0.000 description 20
238000003818 flash chromatography Methods 0.000 description 18
239000003921 oil Substances 0.000 description 18
235000019198 oils Nutrition 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
OYVDXEVJHXWJAE-UHFFFAOYSA-N 5-ethenylpyrrolidin-2-one Chemical compound C=CC1CCC(=O)N1 OYVDXEVJHXWJAE-UHFFFAOYSA-N 0.000 description 17
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
238000002390 rotary evaporation Methods 0.000 description 16
101150041968 CDC13 gene Proteins 0.000 description 15
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 15
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 15
239000002904 solvent Substances 0.000 description 15
238000005160 1H NMR spectroscopy Methods 0.000 description 14
239000007788 liquid Substances 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
239000000284 extract Substances 0.000 description 12
238000000926 separation method Methods 0.000 description 12
229910000104 sodium hydride Inorganic materials 0.000 description 12
239000012071 phase Substances 0.000 description 11
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
238000001816 cooling Methods 0.000 description 10
229920006395 saturated elastomer Polymers 0.000 description 10
239000012312 sodium hydride Substances 0.000 description 10
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
230000010933 acylation Effects 0.000 description 9
239000008346 aqueous phase Substances 0.000 description 9
239000012299 nitrogen atmosphere Substances 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
238000001914 filtration Methods 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
ANBGXGLWQIYNLP-QMMMGPOBSA-N methyl (2s)-2-(benzenesulfonyloxy)propanoate Chemical compound COC(=O)[C@H](C)OS(=O)(=O)C1=CC=CC=C1 ANBGXGLWQIYNLP-QMMMGPOBSA-N 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
229910000027 potassium carbonate Inorganic materials 0.000 description 8
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
230000006181 N-acylation Effects 0.000 description 7
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 7
239000000203 mixture Substances 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
ZQHHVFKRZCLJNC-ZETCQYMHSA-N (2s)-2-methyl-3-oxo-3-phenylpropanoyl chloride Chemical compound ClC(=O)[C@@H](C)C(=O)C1=CC=CC=C1 ZQHHVFKRZCLJNC-ZETCQYMHSA-N 0.000 description 6
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
238000006073 displacement reaction Methods 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
239000002480 mineral oil Substances 0.000 description 6
235000010446 mineral oil Nutrition 0.000 description 6
235000011181 potassium carbonates Nutrition 0.000 description 6
125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
AWYZUBUIFKMOFY-ZETCQYMHSA-N (2s)-2-[tert-butyl(dimethyl)silyl]oxypropanoyl chloride Chemical compound ClC(=O)[C@H](C)O[Si](C)(C)C(C)(C)C AWYZUBUIFKMOFY-ZETCQYMHSA-N 0.000 description 5
XWILORJMRMFKPM-ZCFIWIBFSA-N (4s)-4-aminohepta-5,6-dienoic acid Chemical compound C=C=C[C@@H](N)CCC(O)=O XWILORJMRMFKPM-ZCFIWIBFSA-N 0.000 description 5
239000002178 crystalline material Substances 0.000 description 5
238000010511 deprotection reaction Methods 0.000 description 5
RAWGHPXIJSCHFZ-VIFPVBQESA-N ethyl (2s)-2-methyl-3-oxo-3-phenylpropanoate Chemical compound CCOC(=O)[C@@H](C)C(=O)C1=CC=CC=C1 RAWGHPXIJSCHFZ-VIFPVBQESA-N 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
239000007787 solid Substances 0.000 description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
238000005292 vacuum distillation Methods 0.000 description 5
HQYWTXUZMXWUQB-CYBMUJFWSA-N (2R)-2-(2,4-dibutylphenoxy)propanoyl chloride Chemical compound C(CCC)C1=C(C=CC(=C1)CCCC)O[C@@H](C(=O)Cl)C HQYWTXUZMXWUQB-CYBMUJFWSA-N 0.000 description 4
OFDVSAVRQDOJSU-LLVKDONJSA-N (2r)-2-(3,5-ditert-butylphenoxy)propanoic acid Chemical compound OC(=O)[C@@H](C)OC1=CC(C(C)(C)C)=CC(C(C)(C)C)=C1 OFDVSAVRQDOJSU-LLVKDONJSA-N 0.000 description 4
XEYSXLKRBATYDV-UHFFFAOYSA-N 5-propa-1,2-dienylpyrrolidin-2-one Chemical compound C=C=CC1CCC(=O)N1 XEYSXLKRBATYDV-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 4
238000005660 chlorination reaction Methods 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
YIULUASLCTYFBY-GFCCVEGCSA-N methyl (2r)-2-(3,5-ditert-butylphenoxy)propanoate Chemical compound COC(=O)[C@@H](C)OC1=CC(C(C)(C)C)=CC(C(C)(C)C)=C1 YIULUASLCTYFBY-GFCCVEGCSA-N 0.000 description 4
IILMJCIWJZWFMD-LLVKDONJSA-N o-methyl (2r)-2-(3,5-ditert-butyl-4-hydroxyphenyl)propanethioate Chemical compound COC(=S)[C@H](C)C1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 IILMJCIWJZWFMD-LLVKDONJSA-N 0.000 description 4
BYSFONKODLHDKK-SNVBAGLBSA-N (2r)-2-(3,5-ditert-butyl-4-hydroxyphenyl)propanethioic s-acid Chemical compound SC(=O)[C@H](C)C1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 BYSFONKODLHDKK-SNVBAGLBSA-N 0.000 description 3
PJDFLNIOAUIZSL-RXMQYKEDSA-N (4s)-4-azaniumylhex-5-enoate Chemical compound C=C[C@@H](N)CCC(O)=O PJDFLNIOAUIZSL-RXMQYKEDSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
VULIHENHKGDFAB-UHFFFAOYSA-N Pterolactam Chemical compound COC1CCC(=O)N1 VULIHENHKGDFAB-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
JFLMDZUHGCHDPN-SFHVURJKSA-N [tert-butyl(dimethyl)silyl] (2s)-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoate Chemical compound CC(C)(C)[Si](C)(C)OC(=O)[C@@H](O[Si](C)(C)C(C)(C)C)CC1=CC=CC=C1 JFLMDZUHGCHDPN-SFHVURJKSA-N 0.000 description 3
238000005903 acid hydrolysis reaction Methods 0.000 description 3
150000003862 amino acid derivatives Chemical class 0.000 description 3
239000003480 eluent Substances 0.000 description 3
239000011521 glass Substances 0.000 description 3
150000002500 ions Chemical class 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
PJDFLNIOAUIZSL-UHFFFAOYSA-N vigabatrin Chemical compound C=CC(N)CCC(O)=O PJDFLNIOAUIZSL-UHFFFAOYSA-N 0.000 description 3
CVSPHBJKUVGOMD-LLVKDONJSA-N (2r)-2-(2,4-ditert-butylphenoxy)propanoic acid Chemical compound OC(=O)[C@@H](C)OC1=CC=C(C(C)(C)C)C=C1C(C)(C)C CVSPHBJKUVGOMD-LLVKDONJSA-N 0.000 description 2
HNVAVUFFJZRPAD-MAUKXSAKSA-N (5s)-1-[(2s)-2-(3,5-ditert-butylphenoxy)propanoyl]-5-ethenylpyrrolidin-2-one Chemical compound O([C@@H](C)C(=O)N1C(CC[C@H]1C=C)=O)C1=CC(C(C)(C)C)=CC(C(C)(C)C)=C1 HNVAVUFFJZRPAD-MAUKXSAKSA-N 0.000 description 2
XKPNHROVKBKJLM-MSOLQXFVSA-N (5s)-1-[(2s)-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]-5-ethenylpyrrolidin-2-one Chemical compound C([C@H](O[Si](C)(C)C(C)(C)C)C(=O)N1C(CC[C@H]1C=C)=O)C1=CC=CC=C1 XKPNHROVKBKJLM-MSOLQXFVSA-N 0.000 description 2
XEYSXLKRBATYDV-ZCFIWIBFSA-N (5s)-5-propa-1,2-dienylpyrrolidin-2-one Chemical compound C=C=C[C@@H]1CCC(=O)N1 XEYSXLKRBATYDV-ZCFIWIBFSA-N 0.000 description 2
241000861718 Chloris <Aves> Species 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 2
239000001961 anticonvulsive agent Substances 0.000 description 2
239000012300 argon atmosphere Substances 0.000 description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000006266 etherification reaction Methods 0.000 description 2
LZCLXQDLBQLTDK-BYPYZUCNSA-N ethyl (2S)-lactate Chemical compound CCOC(=O)[C@H](C)O LZCLXQDLBQLTDK-BYPYZUCNSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
238000000605 extraction Methods 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
238000005342 ion exchange Methods 0.000 description 2
239000004310 lactic acid Substances 0.000 description 2
239000010410 layer Substances 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
LPEKGGXMPWTOCB-VKHMYHEASA-N methyl (S)-lactate Chemical compound COC(=O)[C@H](C)O LPEKGGXMPWTOCB-VKHMYHEASA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
235000015320 potassium carbonate Nutrition 0.000 description 2
239000000047 product Substances 0.000 description 2
239000000376 reactant Substances 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
239000002002 slurry Substances 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
230000002194 synthesizing effect Effects 0.000 description 2
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
FVXFWBAJDYXSHV-NVXWUHKLSA-N (5s)-1-[(2r)-2-(2,4-ditert-butylphenoxy)propanoyl]-5-ethenylpyrrolidin-2-one Chemical compound O([C@H](C)C(=O)N1C(CC[C@H]1C=C)=O)C1=CC=C(C(C)(C)C)C=C1C(C)(C)C FVXFWBAJDYXSHV-NVXWUHKLSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
KPZBEZVZFBDKCG-UHFFFAOYSA-N 2,4-dibutylphenol Chemical compound CCCCC1=CC=C(O)C(CCCC)=C1 KPZBEZVZFBDKCG-UHFFFAOYSA-N 0.000 description 1
NFVMNXZFSKGLDR-UHFFFAOYSA-N 2,6-ditert-butyl-4-sulfanylphenol Chemical compound CC(C)(C)C1=CC(S)=CC(C(C)(C)C)=C1O NFVMNXZFSKGLDR-UHFFFAOYSA-N 0.000 description 1
HRUHVKFKXJGKBQ-UHFFFAOYSA-N 3,5-dibutylphenol Chemical compound CCCCC1=CC(O)=CC(CCCC)=C1 HRUHVKFKXJGKBQ-UHFFFAOYSA-N 0.000 description 1
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
244000166102 Eucalyptus leucoxylon Species 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
235000019502 Orange oil Nutrition 0.000 description 1
229910003074 TiCl4 Inorganic materials 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
239000010779 crude oil Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
230000000994 depressogenic effect Effects 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
OYFGNYSKDSIEEB-GFCCVEGCSA-N methyl (2r)-2-(2,4-ditert-butylphenoxy)propanoate Chemical compound COC(=O)[C@@H](C)OC1=CC=C(C(C)(C)C)C=C1C(C)(C)C OYFGNYSKDSIEEB-GFCCVEGCSA-N 0.000 description 1
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
239000010802 sludge Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000007858 starting material Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000725 suspension Substances 0.000 description 1
FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical group CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
ULYLMHUHFUQKOE-UHFFFAOYSA-N trimethyl(prop-2-ynyl)silane Chemical compound C[Si](C)(C)CC#C ULYLMHUHFUQKOE-UHFFFAOYSA-N 0.000 description 1
JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
ORGHESHFQPYLAO-UHFFFAOYSA-N vinyl radical Chemical class C=[CH] ORGHESHFQPYLAO-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 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
- 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
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/22—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from lactams, cyclic ketones or cyclic oximes, e.g. by reactions involving Beckmann rearrangement
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/30—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and unsaturated
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/84—Unsaturated compounds containing keto groups containing six membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrrole Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

IL10036091A 1990-12-17 1991-12-12 HISTORY OF PYROLIDINONE USED AS SUBSTANCE (S) -Vinyl and Alanyl GABA IL100360A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US62873890A	1990-12-17	1990-12-17

Publications (2)

Publication Number	Publication Date
IL100360A0 IL100360A0 (en)	1992-09-06
IL100360A true IL100360A (en)	1998-08-16

Family

ID=24520094

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL10036091A IL100360A (en)	1990-12-17	1991-12-12	HISTORY OF PYROLIDINONE USED AS SUBSTANCE (S) -Vinyl and Alanyl GABA

Country Status (13)

Country	Link
EP (1)	EP0492350B1 (de)
JP (1)	JP3143877B2 (de)
KR (1)	KR920012021A (de)
AT (1)	ATE159246T1 (de)
AU (2)	AU644919B2 (de)
CA (1)	CA2057699C (de)
DE (1)	DE69127960T2 (de)
DK (1)	DK0492350T3 (de)
ES (1)	ES2110974T3 (de)
GR (1)	GR3025831T3 (de)
HU (1)	HU218793B (de)
IE (1)	IE914371A1 (de)
IL (1)	IL100360A (de)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL100360A (en) *	1990-12-17	1998-08-16	Merrell Dow Pharma	HISTORY OF PYROLIDINONE USED AS SUBSTANCE (S) -Vinyl and Alanyl GABA
CA2166061C (en) *	1993-06-23	1999-02-23	Michael H. Kolb	Novel processes for preparing (s)-4-amino-hepta-5,6-dienoic acid and intermediates thereof
ITMI991330A1 (it) *	1999-06-15	2000-12-15	Isagro Spa	Processo per la preparazione di fungicidi otticamente attivi costituiti da n-acil derivati del metil n-(2,6-dimetilfenil)-d-alaninato
CN110713440B (zh) *	2018-07-11	2022-01-25	武汉武药科技有限公司	一种氨己烯酸的制备方法

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3959356A (en) *	1975-03-18	1976-05-25	Richardson-Merrell Inc.	Acetylene derivatives of amino acids
US3960927A (en) *	1975-03-18	1976-06-01	Richardson-Merrell Inc.	Olefinic derivatives of amino acids
GB2120244B (en) *	1982-05-17	1985-05-01	Merrell Toraude & Co	Aminoalkadiene derivative
GB2133002B (en) *	1982-12-30	1986-01-29	Merrell Toraude & Co	Process for preparing 4-amino-5-hexenoic acid
JPS6036448A (ja) *	1983-07-07	1985-02-25	シンテツクス（ユー・エス・エイ）インコーポレイテツド	γ―アレル―γ―アミノ酪酸類
US4912232A (en) *	1983-10-14	1990-03-27	Dow Chemical Company	Preparation of N-hydrocarbylcarbonyl-5-(1-hydrocarbylcarbonyloxy)hydrocarbyl-pyrrolidin-2-one
US4873336A (en) *	1988-03-28	1989-10-10	Gaf Corporation	Process for the preparation of N-vinyl lactams
CA1336333C (en) *	1988-05-20	1995-07-18	Davide Della Bella	Pyrrolidone-2 compounds and their use for central analgesic activity
IL100360A (en) *	1990-12-17	1998-08-16	Merrell Dow Pharma	HISTORY OF PYROLIDINONE USED AS SUBSTANCE (S) -Vinyl and Alanyl GABA

1991
- 1991-12-12 IL IL10036091A patent/IL100360A/en not_active IP Right Cessation
- 1991-12-12 AU AU89635/91A patent/AU644919B2/en not_active Expired
- 1991-12-16 DK DK91121554.9T patent/DK0492350T3/da active
- 1991-12-16 DE DE69127960T patent/DE69127960T2/de not_active Expired - Lifetime
- 1991-12-16 ES ES91121554T patent/ES2110974T3/es not_active Expired - Lifetime
- 1991-12-16 IE IE437191A patent/IE914371A1/en not_active IP Right Cessation
- 1991-12-16 HU HU969/91A patent/HU218793B/hu unknown
- 1991-12-16 AT AT91121554T patent/ATE159246T1/de not_active IP Right Cessation
- 1991-12-16 EP EP91121554A patent/EP0492350B1/de not_active Expired - Lifetime
- 1991-12-16 CA CA002057699A patent/CA2057699C/en not_active Expired - Lifetime
- 1991-12-17 JP JP03352847A patent/JP3143877B2/ja not_active Expired - Lifetime
- 1991-12-17 KR KR1019910023189A patent/KR920012021A/ko not_active Withdrawn
1994
- 1994-01-21 AU AU53900/94A patent/AU658538B2/en not_active Expired
1998
- 1998-01-07 GR GR980400006T patent/GR3025831T3/el unknown

Also Published As

Publication number	Publication date
IE914371A1 (en)	1992-06-17
EP0492350B1 (de)	1997-10-15
DE69127960D1 (de)	1997-11-20
EP0492350A1 (de)	1992-07-01
DE69127960T2 (de)	1998-03-05
CA2057699A1 (en)	1992-06-18
DK0492350T3 (da)	1998-01-26
IL100360A0 (en)	1992-09-06
AU8963591A (en)	1992-06-18
ATE159246T1 (de)	1997-11-15
HU218793B (hu)	2000-12-28
JP3143877B2 (ja)	2001-03-07
JPH04334364A (ja)	1992-11-20
GR3025831T3 (en)	1998-04-30
AU5390094A (en)	1994-03-17
ES2110974T3 (es)	1998-03-01
CA2057699C (en)	2002-10-29
HU913969D0 (en)	1992-02-28
HUT63829A (en)	1993-10-28
AU658538B2 (en)	1995-04-13
KR920012021A (ko)	1992-07-25
AU644919B2 (en)	1993-12-23

Legal Events

Date	Code	Title
1998-12-27	FF	Patent granted
1999-08-17	KB	Patent renewed
2002-02-10	KB	Patent renewed
2006-02-21	KB	Patent renewed
2010-05-31	KB	Patent renewed
2012-07-31	EXP	Patent expired

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WO2018042393A1 (en)	2018-03-08	Novel process for the preparation of brivaracetam
HU199809B (en)	1990-03-28	Process for producing aminomethyl-4,5-dihydroisoxazole derivatives and pharmaceutical compositions comprising same
MXPA02005396A (es)	2002-11-29	Proceso e intermedios quimicos.
MXPA05002874A (es)	2005-05-27	Procedimiento para la sintesis de intermediarios utiles para la sintesis de inhibidores de tubulina.
KR20020060988A (ko)	2002-07-19	시클릭 아미노산의 입체선택적 합성 방법
EP0492350B1 (de)	1997-10-15	Verfahren zur Herstellung von (S)-vinyl- und (S)-allenyl-Gaba
JPH09500131A (ja)	1997-01-07	Ｈｉｖプロテアーゼ阻害剤の製造方法
US5208345A (en)	1993-05-04	Process for the production of (S)-vinyl and allenyl gaba
Micouin et al.	1996	Asymmetric synthesis. XXXIX. 1 Synthesis of 3-substituted piperidin-2-ones from chiral non-racemic lactams
WO2002012230A1 (en)	2002-02-14	Intermediate of carbapenem antibiotics and process for the preparation thereof
JPS5936914B2 (ja)	1984-09-06	セフアロスポリン類縁体
JPS6328423B2 (de)	1988-06-08
KR0136706B1 (ko)	1998-04-25	광학 활성이 있는 3-아미노 피롤리딘 유도체의 제조방법
EP0316360A1 (de)	1989-05-24	Asymmetrische synthese von enantiomerisch reinen monocyclischen beta-lactam-zwischenprodukten
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KR20010043475A (ko)	2001-05-25	순수 이성체 다중 치환된 아자시클릭 화합물의 입체화학조절적 제조방법
JP4157175B2 (ja)	2008-09-24	２′−ピロリジンプロパン酸誘導体の製造方法
JPH08143517A (ja)	1996-06-04	光学活性３−アミノ−１，２−ブタンジオール誘導体の製造法
JP2818890B2 (ja)	1998-10-30	アリルアミン化合物の製造方法および同化合物の製造用中間体の製造方法
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