Two novel methods have been developed for the preparation of 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl]acetamide ((R)-Phenotropil). In the first, n-butyl (3R)-4-amino-3-phenylbutyrate is alkylated with haloacetamide in DMF in the presence of potassium phosphate monohydrate, and the intermediate 4-carbamoylmethylamino-3-phenylbutyrate is subsequently cyclized by refluxing in toluene in the presence of potassium phosphate monohydrate and tetrabutylammonium bromide. In the second, chloroacetonitrile is used under similar conditions in place of the haloacetamide. Both methods lead to (R)-Phenotropil in 40-60% yields calculated on the starting n-butyl (3R)-4-amino-3-phenylbutyrate.

中文翻译：

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合成2-[（（4 R）-2-氧代-4-苯基吡咯烷基-1-基]-乙酰胺（（R）-phenotropil）的新方法

已经开发出两种新颖的方法来制备2-[（（4 R）-2-氧--4-苯基吡咯烷-1-基]乙酰胺（（R -Phenotropil））。首先，在磷酸一水合物存在下，在DMF中用卤代乙酰胺将（3 R）-4-氨基-3-苯基丁酸正丁酯烷基化，然后通过在甲苯中回流将中间体4-氨基甲酰基甲基氨基-3-苯基丁酸环化。在磷酸钾一水合物和四丁基溴化铵存在下。第二，在相似条件下使用氯乙腈代替卤代乙酰胺。这两种方法都导致（[R）-Phenotropil在起始计算40-60％的产率Ñ丁基（3 - [R）-4-氨基-3-苯基丁酸酯。