Hypolipaemic bis-para-chloro-phenoxy-acetic acid prodn. - from sodium chloro-phenolate prepd. by reaction of chlorophenol with sodium hydroxide with azeotropic removal of water (OE 15.2.80)

摘要

In the prodn. of bis(p-chlorophenoxy)acetic acid (I), (A) a soln. of sodium p-chloro-phenolate is prepd. by reaction of p-chlorophenol with NaOH with azeotropic removal of water in a solvent mixt. of a 3-6C alcohol and a hydrocarbon of b.pt. 80-150 degrees C; (B) reacting the soln. at reflux with a dichloroacetic acid ester; (C) washing pptd. NaCl with water; (D) hydrolysing the reaction mixt. with NaOH with complete removal of the organic solvent by distn.; (E) pptg. (I) by addn. of dil. mineral acid and filtering it off; and (F) purifying the prod. by reprecipitation and/or recrystallisation. (I) is an orally active agent for lowering serum lipid and cholesterol levels. Simple process avoiding the use of metallic sodium or of NaH and giving pure (I) in up to 90% yield. The p-chlorophenol starting material need only be of technical grade.