(4-Chlorophenyl)acetic acid → 4-Chlorophenylacetyl chloride

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Reaction Steps

For example, 4-chlorophenylacetic acid 1, can be treated with thionyl chloride to activate the carboxylic acid. This can then be treated with bromine to form 4-chlorophenylacetyl chloride. The esterification is conveniently carried out with (S)—N,N-tetramethylenelactamide 2. This reaction sequence is particularly advantageous as the reactions are conveniently carried out in one reaction vessel with only one isolation step. The displacement reaction of ester 3 with 3-trifluoromethylphenol 4 in the presence of potassium hydroxide gives α-(phenoxy)phenylacetic acid ester 5. Hydrolysis of the α-(phenoxy)phenylacetic acid ester 5 with lithium hydroxide afforded α-(phenoxy)phenylacetic acid 6. In this manner, (4-chlorophenyl)-(3-trifluoromethylphenoxy)-acetic acid, i.e., CPTA, can be prepared in five steps in about 73% yield following crystallization from heptane.

Provenance & Evidence