| 摘要 |
A process for the preparation of trifluoroethoxy benzoic acid derivatives, in particular Flecainide, and their pharmaceutically acceptable salts, starting with commercially available halobenzoic acids and involving the use of simple reagents and low cost solvents, to afford high overall yield of the product. The above object is achieved in accordance with the present invention which, in one aspect thereof, provides a process for preparing a compound of formula (A): and pharmaceutically acceptable salts thereof, which process comprises the steps of: a) reacting a halobenzoic acid or a salt thereof of the formula [II] with 2,2,2-trifluoroethanol in the presence of a strong base and a copper containing material, if desired followed by acidification to obtain a compound of formula [I] b) converting the product obtained in step a) above into the compound of formula (A) or a pharmaceutically acceptable salt thereof. wherein Ar, R, n and m are as defined above; M is hydrogen or a metal, ammonium or phosphonium cation; and X is Cl, Br or 1, and when n>1 the X substituents may be the same or different; With 2,2,2-trifuoroethanol in the presence of a strong base and a copper containing material, if desired followed by acidification to obtain a compound of formula [I] wherein Ar, R m and n are as defined above, and (b) converting the product in step a) above into the compound of formula (A) or a pharmaceutically acceptable salt thereof.
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