Optically active sulpiride is prepared by converting levo-proline (I) to the correspondig levorotatory acetylproline (II), followed by reduction, chlorination and amination to afford levorotatory N-ethyl-2-aminomethylpyrrolidine (V), which, upon treatment with an ester of 2-methoxy-5-sulfamoylbenzoic acid (VI), yields N-(1-ethyl-2-pyrrolidinomethyl)-2-methoxy-5-sulfamoylbenzamide, that is, the levorotatory enantiomer of sulpiride.

This compound is obtained by condensation of 2(S)-(aminomethyl)-1-ethylpyrrolidine (I) with 5-(aminosulfonyl)-2-methoxybenzoyl chloride (II) by means of K2CO3 in acetone. The starting compounds (I) and (II) are obtained as follows: a) The acylation of 2(S)-(hydroxymethyl)pyrrolidine (III) with acetic anhydride in refluxing methanol gives 1-acetyl-2(S)-(hydroxymethyl)pyrrolidine (IV), which by reaction with SOCl2 in CHCl3 is converted into 1-acetyl-2(S)-(chloromethyl)pyrrolidine (V). The reaction of (V) with sodium azide in hot DMF affords the corresponding azide (VI), which is reduced with LiAlH4 in refluxing THF to yield the desired product (I). b) The methylation of 2-hydroxybenzaldehyde (VII) with dimethyl sulfate and K2SO3 in refluxing acetone gives 2-methoxybenzaldehyde (VIII), which is oxidized with KMnO4 in hot aqueous NaOH affording 2-methoxybenzoic acid (IX). The sulfonation of (IX) with hot chlorosulfonic acid yields 5-(chlorosulfonyl)-2-methoxybenzoic acid (X), which is finally treated with 28% aqueous NaOH to give the desired product (II).