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【结 构 式】 
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【分子编号】11269 【品名】(2S)-2-(2-Oxo-1-pyrrolidinyl)butyric acid 【CA登记号】102849-49-0 |
【 分 子 式 】C8H13NO3 【 分 子 量 】171.19616 【元素组成】C 56.13% H 7.65% N 8.18% O 28.04% |
合成路线1
该中间体在本合成路线中的序号：(VIII)An alternative procedure involves hydrolysis of racemic ethyl 2-(2-oxopyrrolidin-1-yl)burytate (VI) with sodium hydroxide to give racemic 2-(2-oxopyrrolidin-1-yl)butyric acid (VII), which is resolved by fractional crystallization with (R)-(+)-alpha-methylbenzylamine in benzene, followed by acid-base treatment to give (S)-2-(2-oxopyrrolidin-1-yl)butyric acid (VIII). Compound (VIII) is finally treated with ethyl chloroformiate and ammonia in dichloromethane.
| 【1】 Cossement, E.; Motte, G.; Geerts, J.-P.; Gobert, J. (UCB SA); The preparation of S-alpha-ethyl-2-oxo-1-pyrrolidineacetamide. GB 2225322 . |
| 【2】 Castaner, J.; Prous, J.; Mealy, N.; Levetiracetam. Drugs Fut 1994, 19, 2, 111. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 10039 | (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine | 3886-69-9 | C8H11N | 详情 | 详情 |
| (VI) | 11267 | ethyl 2-(2-oxo-1-pyrrolidinyl)butanoate | C10H17NO3 | 详情 | 详情 | |
| (VII) | 11268 | 2-(2-Oxo-1-pyrrolidinyl)butyric acid | 67118-31-4 | C8H13NO3 | 详情 | 详情 |
| (VIII) | 11269 | (2S)-2-(2-Oxo-1-pyrrolidinyl)butyric acid | 102849-49-0 | C8H13NO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Reaction of (S)-2-aminobutyramide (I) with ethyl 4-bromobutyrate (II) in the presence of triethylamine in toluene gives ethyl (S)-4-[1-(carbamoyl)propylamino]butyrate (III), which is cyclized in toluene by means of 2-hydroxypyridine. Compound (I) can also be condensed with 4-chlorobutyryl chloride (IV) either directly in the presence of tetrabutylammonium bromide (TBAB) in dichloromethane, followed by in situ treatment with potassium hydroxide, or via the isolation of intermediate (S)-N-[1-(carbamoyl)propyl]-4-chlorobutyramide (V). An alternative procedure involves hydrolysis of racemic ethyl 2-(2-oxopyrrolidin-1-yl)butyrate (VI) with sodium hydroxide to give racemic 2-(2-oxopyrrolidin-1-yl)butyric acid (VII), which is resolved by fractional crystallization with (R)-(+)-alpha-methylbenzylamine in benzene, followed by acid-base treatment to give (S)-2-(2-oxopyrrolidin-1-yl)butyric acid (VIII). Compound (VIII) is finally treated with ethyl chloroformiate and ammonia in dichloromethane. A third procedure involves Ni-Raney desulfurization of (S)-4-(methylthio)-2-(2-oxopyrrolidin-1-yl)butyramide (XI), prepared from (S)-2-amino-4-(methylthio)butyramide (IX) by reaction with 4-chlorobutyryl chloride (IV). Compound (XI) can also be obtained by treatment of (IX) with ethyl 4-bromobutyrate (II) to give ethyl (S)-4-[1-(carbamoyl)-3-(methylthio)propylamino]butyrate (X), which is cyclized in toluene by means of 2-hydroxypyridine.
| 【1】 Gobert, J.; Geerts, J.-P.; Bodson, G. (UCB SA); (S)-alpha-Ethyl-2-oxopyrrolidineacetamide. AU 8542530; EP 0162036; ES 8608485; ES 8704893; US 4696943; US 4837223 . |
| 【2】 Cossement, E.; Motte, G.; Geerts, J.-P.; Gobert, J. (UCB SA); The preparation of S-alpha-ethyl-2-oxo-1-pyrrolidineacetamide. GB 2225322 . |
| 【3】 Castaner, J.; Prous, J.; Mealy, N.; Levetiracetam. Drugs Fut 1994, 19, 2, 111. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10039 | (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine | 3886-69-9 | C8H11N | 详情 | 详情 | |
| (VII)-rac | 11268 | 2-(2-Oxo-1-pyrrolidinyl)butyric acid | 67118-31-4 | C8H13NO3 | 详情 | 详情 |
| (I) | 11262 | (2S)-2-Aminobutanamide | C4H10N2O | 详情 | 详情 | |
| (II) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
| (III) | 11264 | ethyl 4-[[(1S)-1-(aminocarbonyl)propyl]amino]butanoate | C10H20N2O3 | 详情 | 详情 | |
| (IV) | 11265 | 4-Chlorobutanoyl chloride; 4-Chlorobutyric acid chloride | 4635-59-0 | C4H6Cl2O | 详情 | 详情 |
| (V) | 11266 | (2S)-2-[(4-Chlorobutanoyl)amino]butanamide | C8H15ClN2O2 | 详情 | 详情 | |
| (VI) | 11267 | ethyl 2-(2-oxo-1-pyrrolidinyl)butanoate | C10H17NO3 | 详情 | 详情 | |
| (VIII) | 11269 | (2S)-2-(2-Oxo-1-pyrrolidinyl)butyric acid | 102849-49-0 | C8H13NO3 | 详情 | 详情 |
| (IX) | 11270 | (2S)-2-Amino-4-(methylsulfanyl)butanamide | C5H12N2OS | 详情 | 详情 | |
| (X) | 11271 | ethyl 4-[[(1S)-1-(aminocarbonyl)-3-(methylsulfanyl)propyl]amino]butanoate | C11H22N2O3S | 详情 | 详情 | |
| (XI) | 11272 | (2S)-4-(Methylsulfanyl)-2-(2-oxo-1-pyrrolidinyl)butanamide | C9H16N2O2S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：（VIII）
| 【1】 Kotkar SP, Sudalai A 2006. A short enantioselective synthesis of the antiepileptic agent, levetiracetam based on proline-catalyzed asymmetric α-aminooxylation Tetrahedron Lett, 47 (38): 6813～ 6815. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| （VI） | 66491 | (S)-1-(1-(benzyloxy)butan-2-yl)pyrrolidin-2-one | C16H23NO | 详情 | 详情 | |
| （VII) | 66492 | (S)-1-(1-hydroxybutan-2-yl)pyrrolidin-2-one | C8H15NO2 | 详情 | 详情 | |
| （VIII） | 11269 | (2S)-2-(2-Oxo-1-pyrrolidinyl)butyric acid | 102849-49-0 | C8H13NO3 | 详情 | 详情 |
| (I) | 66487 | (S)-2-((phenylamino)oxy)butan-1-ol | C10H15NO2 | 详情 | 详情 | |
| (II) | 66488 | (S)-butane-1,2-diol | 40348-66-1 | C4H10O2 | 详情 | 详情 |
| (III) | 66489 | (S)-1-(benzyloxy)butan-2-ol | C11H16O2 | 详情 | 详情 | |
| (IV) | 66490 | (S)-1-(benzyloxy)butan-2-yl methanesulfonate | C12H18O4S | 详情 | 详情 | |
| (V) | 27397 | 2-Pyrrolidinone | 616-45-5 | C4H7NO | 详情 | 详情 |