PREPARING (S)-5-HYDROXYMETHYL-3-ISOPROPYLOXAZOL-IDIN-2-ONE SULPHONIC ACID ESTER AND ITS USE IN PREPARING S-METOPROLOL

摘要

A process for preparing S-metoprolol of the formula or a salt thereof, with high enantiomeric purity, is described, whereby a (S)-5-hydroxymethyl-3-isopropyloxazolidin-2-one sulfonic acid ester of the formula is prepared, and further reacted with 4-[2-methoxyethyl]phenol of the formula and the resulting intermediate of the formula is hydrolysed to S-metoprolol, and whereby the (S)-5-hydroxymethyl-3-isopropyloxazolidin-2-one sulfonic acid ester of formula II is prepared by reacting (S)-3-isopropylamino-1,2-propanediol of the formula with a chloroformic acid ester of the formula Cl- @-OR min VI wherein R min is an alkyl group having 1-3 carbon atoms or a phenyl group, to the formation of (S)-5-hydroxymethyl-3-isopropyloxazolidin-2-one of the formula which is reacted with an activated sulfonic acid of the formula wherein R sec is an aryl group such as tolyl and X is a halogen such as Cl, to formation of the ester of formula II, which when required is enriched with the (S)-enantiomer by crystallization.