The invention discloses a preparation method of (S)-1-(2-chloracetyl)
pyrrolidine-2-carbonitrile, which is applied to the field of
chemical synthesis. The preparation method comprises the following steps of (1) dropwise adding chloracetyl
chloride into a
mixed solution composed of L-prolinamide, organic alkali and
dichloromethane, and reacting after finishing the dropwise adding operation to obtain a reaction solution I containing 1-chloroacetylpyrrolidine-2-
carboxamide; and (2) enabling the reaction solution I to react with
phosphorus oxychloride serving as a dehydrating agent to obtain (S)-1-(2-chloracetyl)
pyrrolidine-2-carbonitrile. In the step (1), the temperature of the
mixed solution I composed of L-prolinamide, organic alkali and
dichloromethane ranges from 10 DEG C below zero to 60 DEG C, the temperature of reaction carried out after the dropwise adding operation is finished ranges from 50 DEG C below zero to 10 DEG C below zero, the reaction carried out after the dropwise adding operation is finished lasts for 0.5-4h, and the
molar ratio of L-prolinamide to chloracetyl
chloride is 1:(1.05-1.31). The preparation method is short in
reaction step and simple in operation and has the advantages that the
raw material cost is low, the yield is high, the product quality is good, little environment
pollution can be caused, green resources can be favorably protected, the required equipment is simple, and the dosage of the used
organic solvent is low.