EP0699672A1 — Process for preparing benzoic acid derivative intermediates and benzothiophene pharmaceutical agents

USPTO Abstract

The present invention provides a novel process for preparing novel compounds of formula I wherein    R¹ and R each are independently C₁-C₄ alkyl, or combine to form piperidinyl, pyrrolidinyl, methylpyrrolidinyl, dimethylpyrrolidinyl, morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; and    n is 2 or 3; or a pharmaceutically acceptable salt thereof, comprising a) reacting a haloalkyl amine of formula III wherein    X is a halogen; and    R¹, R, and n are as defined above, with a compound of formula IV wherein R is C₁-C₆ alkyl, in the presence of an alkyl acetate solvent and a base; b) extracting the reaction product of step a) with an aqueous acid; and c) cleaving the ester of the reaction product from step b) to form an acid. The present invention further provides a novel process for preparing compounds of formula V wherein    R¹ and R each are independently C₁-C₄ alkyl, or combine to form piperidinyl, pyrrolidino, methylpyrrolidino, dimethylpyrrolidinyl, morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino;    R³ and R⁴ each are H or a hydroxy protecting group; and    n is 2 or 3; or a pharmaceutically acceptable salt thereof, comprising a) reacting a haloalkyl amine of formula III wherein    X is a halogen; and    R¹, R, and n are as defined above, with a compound of formula IV wherein R is C₁-C₆ alkyl, in the presence of an alkyl acetate solvent and a base; b) extracting the reaction product from step a) with an aqueous acid; c) cleaving the ester of the reaction product from step b) to form an acid; d) reacting the extracted product from step c) with a compound of formula V wherein R³ and R⁴ are as defined above, or a pharmaceutically acceptable salt thereof; e) optionally removing the R³ and R⁴ hydroxy protecting groups of the reaction product form step d); and f) optionally forming a salt of the reaction product from either steps d) or step e).