IL100360A - HISTORY OF PYROLIDINONE USED AS SUBSTANCE (S) -Vinyl and Alanyl GABA - Google Patents
HISTORY OF PYROLIDINONE USED AS SUBSTANCE (S) -Vinyl and Alanyl GABAInfo
- Publication number
- IL100360A IL100360A IL10036091A IL10036091A IL100360A IL 100360 A IL100360 A IL 100360A IL 10036091 A IL10036091 A IL 10036091A IL 10036091 A IL10036091 A IL 10036091A IL 100360 A IL100360 A IL 100360A
- Authority
- IL
- Israel
- Prior art keywords
- solution
- mmol
- nmr
- chloride
- added
- Prior art date
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)
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 (fr) |
| JP (1) | JP3143877B2 (fr) |
| KR (1) | KR920012021A (fr) |
| AT (1) | ATE159246T1 (fr) |
| AU (2) | AU644919B2 (fr) |
| CA (1) | CA2057699C (fr) |
| DE (1) | DE69127960T2 (fr) |
| DK (1) | DK0492350T3 (fr) |
| ES (1) | ES2110974T3 (fr) |
| GR (1) | GR3025831T3 (fr) |
| HU (1) | HU218793B (fr) |
| IE (1) | IE914371A1 (fr) |
| IL (1) | IL100360A (fr) |
Families Citing this family (4)
| 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 |
| WO1995000470A1 (fr) * | 1993-06-23 | 1995-01-05 | Merrell Pharmaceuticals Inc. | Nouveaux procedes de preparation d'acide (s)-4-amino-hepta-5,6-dienoique et des intermediaires de celui-ci |
| 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)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3960927A (en) * | 1975-03-18 | 1976-06-01 | Richardson-Merrell Inc. | Olefinic derivatives of amino acids |
| US3959356A (en) * | 1975-03-18 | 1976-05-25 | Richardson-Merrell Inc. | Acetylene 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 |
| NO842759L (no) * | 1983-07-07 | 1985-01-08 | Syntex Inc | Fremgangsmaate ved fremstilling av nye, terapeutisk virksomme gamma-allenyl-gamma-aminosmoersyrer |
| 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 |
| IE61631B1 (en) * | 1988-05-20 | 1994-11-16 | Zambon Spa | Compounds with central analgesic activity, process for their preparation and pharmaceutical compositions containing them |
| 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 CA CA002057699A patent/CA2057699C/fr not_active Expired - Lifetime
- 1991-12-16 ES ES91121554T patent/ES2110974T3/es not_active Expired - Lifetime
- 1991-12-16 HU HU969/91A patent/HU218793B/hu unknown
- 1991-12-16 DE DE69127960T patent/DE69127960T2/de not_active Expired - Lifetime
- 1991-12-16 EP EP91121554A patent/EP0492350B1/fr not_active Expired - Lifetime
- 1991-12-16 IE IE437191A patent/IE914371A1/en not_active IP Right Cessation
- 1991-12-16 DK DK91121554.9T patent/DK0492350T3/da active
- 1991-12-16 AT AT91121554T patent/ATE159246T1/de not_active IP Right Cessation
- 1991-12-17 KR KR1019910023189A patent/KR920012021A/ko not_active Application Discontinuation
- 1991-12-17 JP JP03352847A patent/JP3143877B2/ja not_active Expired - Lifetime
-
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 |
|---|---|
| GR3025831T3 (en) | 1998-04-30 |
| KR920012021A (ko) | 1992-07-25 |
| CA2057699A1 (fr) | 1992-06-18 |
| IE914371A1 (en) | 1992-06-17 |
| AU8963591A (en) | 1992-06-18 |
| HU913969D0 (en) | 1992-02-28 |
| DK0492350T3 (da) | 1998-01-26 |
| EP0492350A1 (fr) | 1992-07-01 |
| EP0492350B1 (fr) | 1997-10-15 |
| IL100360A0 (en) | 1992-09-06 |
| JP3143877B2 (ja) | 2001-03-07 |
| DE69127960T2 (de) | 1998-03-05 |
| DE69127960D1 (de) | 1997-11-20 |
| ES2110974T3 (es) | 1998-03-01 |
| HUT63829A (en) | 1993-10-28 |
| AU644919B2 (en) | 1993-12-23 |
| AU5390094A (en) | 1994-03-17 |
| CA2057699C (fr) | 2002-10-29 |
| AU658538B2 (en) | 1995-04-13 |
| JPH04334364A (ja) | 1992-11-20 |
| HU218793B (hu) | 2000-12-28 |
| ATE159246T1 (de) | 1997-11-15 |
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| EXP | Patent expired |