Processes for the preparation of 4′-[3-[4-(6-Fluoro-1 ,2-benzisoxazol-3-yl)piperidino]propoxy]-3′-methoxyacetophenone and intermediates thereof

摘要

The present invention relates to processes for the preparation of 4′-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidino]propoxy]-3′-methoxyacetophenone and intermediates thereof. The present invention also provides a process for purifying 4′-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidino]propoxy]-3′-methoxyacetophenone to obtain the purity greater than about 98.0 area % to about 99.0 area % as measured by HPLC, preferably greater than about 99.0 area % to about 99.5 area %, more preferably greater about 99.5 area % to about 99.9 area %. individual impurities lower than about 0.15 area %, preferably lower than about 0.1% and total impurities lower than about 0.5 area % by HPLC.

主权项

1. A process for preparing intermediate 4-(31-propoxy)-3-methoxyacetophenone compound of formula (II): wherein X is a leaving group selected from halogen, methanesulphonate, benzenesulphonate, p-toluenesulphonate, 4-nitrobenzene sulphonate, 4-bromobenzene sulphonate and trifluoromethyl sulphonate, comprising:
reacting 1-[4-(31-propoxy)-3-methoxyphenyl]ethanol of formula (III): where X is as defined above;with an oxidizing agent, optionally in the presence of a solvent, wherein the oxidizing agent is selected from the group consisting of collin's reagent, pyridinium dichromate, pyridinium chlorochromate, pyridinium chlorochromate on alumina, DMSO-DCC, DMSO-acetic anhydride or mixtures thereof.