首页> 外国专利> IMPROVED PROCESS FOR THE PREPARATION OF (S)-ALPHA-ETYL-2-OXO-1-PYRROLIDINEACETAMIDE AND (R)-ALPHA-ETHYL-2-OXO-1-PYRROLIDINEACETAMIDE

IMPROVED PROCESS FOR THE PREPARATION OF (S)-ALPHA-ETYL-2-OXO-1-PYRROLIDINEACETAMIDE AND (R)-ALPHA-ETHYL-2-OXO-1-PYRROLIDINEACETAMIDE

机译:(S)-α-乙基-2-乙基-氧代-1-乙酰胺化酰胺和(R)-α-乙基-2-氧--1-氧代乙酰胺化酰胺的制备方法得到改进

摘要

A process provided for the preparation of the (S)- and (R)- alpha- ethyl-2-oxo-1- pyrrolidineacetamide of formula:(1) from (RS)-alpha-ethyl-2-oxo-l-pyrrolidineacetic acid of formula:(2) comprising: i) combining the (RS)-2 with a chiral base (resolving agent) in a resolution solvent and crystallizing from the said mixture the diastereomeric salt of (S)- or (R)-2 and chiral base; ii) regenerating (S)- or (R)-2 from the crystallized diastereomeric salt by treating with a suitable acid or acidic ion-exchange resin; iii) optionally regenerating (R)- or (S)-2 or their mixture (predominantly one enantiomer) from the crystallization mother liquor by treating with a suitable acid or acidic ion-exchange resin; iv) optionally epimerizing (RS)-2 by treating (R)- or (S)-2 or their mixture (predominantly one enantiomer) of step iii with an acid anhydride; V) optionally converting (RS)-2 of step iv into enantiomerically enriched (S)- or (R)-2 through steps i and ii; vi) formation of the mixed anhydride by reacting (R)- or (S)-2 with an alkyl or aryl sulfonyl halogen compound RSO2X in the presence of a suitable base; and vii) reacting the mixed anhydride with ammonia; wherein R represents C 1 to C 15 alkyl or aryl groups such as methyl, ethyl, p-toluenyl, 2,4,6-trimethylbenzyl, 2,4,6-trichloribenzyl, and X represents a halogen atom such as F, Cl and Br atoms.
机译:提供一种由(RS)-α-乙基-2-氧代-1-吡咯烷乙酸制备式(1)的(S)-和(R)-α-乙基-2-氧代-1-吡咯烷乙酰胺的方法式(2)的酸,其包括:i)在拆分溶剂中将(RS)-2与手性碱(拆分剂)合并,并从所述混合物中结晶出(S)-或(R)-2的非对映异构体盐。和手性碱; ii)通过用合适的酸或酸性离子交换树脂处理,从结晶的非对映体盐再生(S)-或(R)-2; iii)通过用适当的酸或酸性离子交换树脂处理,任选地从结晶母液中再生(R)-或(S)-2或其混合物(主要是一种对映异构体); iv)通过用酸酐处理步骤iii的(R)-或(S)-2或它们的混合物(主要是一种对映异构体)来任选地差向异构化(RS)-2; V)通过步骤i和ii任选地将步骤iv的(RS)-2转化为对映体富集的(S)-或(R)-2; vi)在合适的碱存在下,通过使(R)-或(S)-2与烷基或芳基磺酰基卤素化合物RSO2X反应形成混合酸酐; vii)使混合酸酐与氨反应;其中R代表C 1至C 15烷基或芳基,例如甲基,乙基,对甲苯基,2,4,6-三甲基苄基,2,4,6-三氯苄基,X代表卤素原子,例如F,Cl和溴原子。

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