Pure methyl 2-acetamido-3-chloropropionate preparation for use as intermediate for hypotensive agent ramipril, from methyl serinate hydrochloride by chlorination, acetylation and purification

摘要

Preparation and purification of methyl 2-acetamido-3-chloropropionate (I) involves: (a) chlorinating methyl serinate hydrochloride (II) with thionyl chloride in an aprotic solvent at elevated temperature; (b) acetylating the obtained methyl 2-amino-3-chloropropionate hydrochloride (III) in the same solvent without isolation, by adding acetyl chloride at elevated temperature; (c) treating the solution with activated carbon and filtering; and (d) stirring the obtained (I) with a 1-4C alcohol.