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【结 构 式】 
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【分子编号】69049 【品名】ethyl 4-amino-3-propylbutyrate hydrochloride;ethyl 3-(aminomethyl)hexanoate hydrochloride 【CA登记号】 |
【 分 子 式 】C9H19NO2.HCl 【 分 子 量 】209.71604 【元素组成】C 51.55% H 9.61% Cl 16.91% N 6.68% O 15.26% |
合成路线1
该中间体在本合成路线中的序号：(XXXI)Conjugate addition of nitromethane to 2-hexenoic acid ethyl ester (XXVII) by means of DBU gives ethyl 2-(nitromethyl)hexanoate (XXVIII), which by nitro group reduction with H2 and Raney-Ni in MeOH at 55 °C cyclizes to the racemic lactam (XXIX). Resolution of compound (XXIX) using chiral column chromatography results in the optically pure (R)-enantiomer (X) .
The intermediate pyrrolidinone butyric acid (IX) can be obtained by N-alkylation of 4-propyl-2-pyrrolidinone (XXIX) with (R)-2-bromobutyric acid (XXX) in the presence of NaH in THF .
In an alternative procedure, alkylation of ethyl 4-amino-3-propylbutyrate hydrochloride (XXXI) with methyl (R)-2-bromobutyrate (XXXII) by means of K2CO3 in acetonitrile gives the amino diester (XXXIII), which cyclizes to the pyrrolidinone (XXXIV) by heating in toluene at 80 °C in the presence of a catalytic amount of 2-hydroxypyridine. Finally, saponification of methyl ester (XXXIV) using aqueous NaOH then affords the corresponding carboxylic acid (IX) .
| 【1】 Surtees, J., Bouvy, D., Thomas, A., Combret, Y., Frank, M., Schmidt, G. (UCB SA). Process for the preparation of 2-oxo-1-pyrrolidine derivatives. EP 1806339. |
| 【2】 Ates, C., Lurquin, F., Quesnel, Y., Schule, A. (UCB SA). 4-Substituted pyrrolidin-2-ones and their use. EP 1926710, JP 2009507870, US 2009318708, WO 2007031263. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 69032 | (2S)-2-(2-oxo-4-propylpyrrolidin-1-yl)butanoic acid | C11H19NO3 | 详情 | 详情 | |
| (X) | 69034 | 4(R)-propyl-2-pyrrolidinone | C7H13NO | 详情 | 详情 | |
| (XXVII) | 69045 | 2-hexenoic acid ethyl ester;trans-2-hexenoic acid ethyl ester;ethyl (E)-hex-2-enoate | 27829-72-7 | C8H14O2 | 详情 | 详情 |
| (XXVIII) | 69046 | ethyl 3-(nitromethyl)hexanoate | C9H17NO4 | 详情 | 详情 | |
| (XXIX) | 69047 | 4-propylpyrrolidin-2-one | C7H13NO | 详情 | 详情 | |
| (XXX) | 69048 | (R)-2-bromobutyric acid;(R)-2-Bromobutyricacid;D-2-Bromobutanoic acid | 2681-94-9 | C4H7BrO2 | 详情 | 详情 |
| (XXXI) | 69049 | ethyl 4-amino-3-propylbutyrate hydrochloride;ethyl 3-(aminomethyl)hexanoate hydrochloride | C9H19NO2.HCl | 详情 | 详情 | |
| (XXXII) | 69050 | methyl (R)-2-bromobutyrate | C5H9BrO2 | 详情 | 详情 | |
| (XXXIII) | 69051 | methyl 3-((((R)-1-methoxy-1-oxobutan-2-yl)amino)methyl)hexanoate | C13H25NO4 | 详情 | 详情 | |
| (XXXIV) | 69052 | (2R)-methyl 2-(2-oxo-4-propylpyrrolidin-1-yl)butanoate | C12H21NO3 | 详情 | 详情 |