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Synthesis of 5-chloro-8-hydroxy-6-methoxy-3-pentylisocoumarin.

Journal of Asian natural products research (2011-05-31)
Aamer Saeed
ABSTRACT

The synthesis of title isocoumarin, the 5-chloro analog of naturally occurring 7-chloro-8-hydroxy-6-methoxy-3-pentylisocoumarin, isolated from Tessmannia densiflora is described. Chlorination of ethyl 2-(2-ethoxy-2-oxoethyl)-4,6-dimethoxybenzoate (2) afforded 3-chloro ester (3) followed by hydrolysis to furnish the 2-(carboxymethyl)-3-chloro-4,6-dimethoxybenzoic acid (4) that was converted to corresponding anhydride (5). Condensation of the latter with hexanoyl chloride in the presence of tetramethylguanidine and triethyl amine afforded 5-chloro-6,8-dimethoxy-3-pentylisocoumarin (6) which upon regioselective demethylation yielded the title isocoumarin (1).

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hexanoyl chloride, ≥99%
Sigma-Aldrich
Hexanoyl chloride, purum, ≥98.0% (GC)
Sigma-Aldrich
Hexanoyl chloride, 97%