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【结 构 式】

【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information