An Improved Synthesis of Metoclopramide

This report relates to a new industrial synthesis of metoclopramide (I). Methyl 4-amino-2-methoxybenzoate (V) was prepared by methylation of p-aminosalicylic acid (III) using dimethyl sulfate in the presence of potassium hydroxide in acetone. V and it's saponified product (VI) were chlorinated with iodobenzene dichloride to obtain methyl 4-amino-5-chloro-2-methoxybenzoate (VII) and 4-amino-5-chloro-2-methoxybenzoic acid (VIII) respectively. VIII was also prepared by saponification of VII. VIII was condensed direct with N, N-diethylethylenediamine (IV), of which amino group was activated by phosphorus trichloride, whereby I was obtained in high yields.