Abstract:

Enantioenriched (S)-3-chloro-1,2-propanediol and (R)-epichlorohydrin were obtained from the kinetic hydrolysis resolution of racemic epichlorohydrin by (S,S)-salen Co(Ⅲ)OAc. (S)-Metoprolol with optical purity higher than 99% could be prepared via the reaction of 4-(2-methoxyethyl)phenol with (S)-3-chloro-1,2-propanediol followed by an amination reaction using isopropyl amine. When (R)-epichlorohydrin was used as the chiral precursor, (S)-metoprolol could be also prepared but with less optical purity(＞92%). The overall yield of (S)-metoprolol was 53.9%. The structure of the product was determined by IR, 1H NMR, 13C NMR and MS. This procedure is effective, simple and has a high utilization rate of raw material. The optical purity and yield of the product are satisfactory. The process is promising for scaling-up industrial potential applications.

Key words: (S)-metoprolol, racemic epichlorohydrin, catalyzed hydrolysis resolution, (R)-epichlorohydrin, (S)-chloro-propanediol, asymmetric synthesis