Phosgene → (E)-5-(2,2-Difluoro-hex-5-ynoyloxymethylene)-2,4-dioxo-thiazolidine-3-carboxylic acid 5-chloro-thiophen-2-ylmethyl Ester

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Reaction Steps

To a stirred solution of (E)-5-(2,2-difluoro-hex-5-ynoyloxymethylidenyl)-2,4-thiazolidindione, which may be prepared as described in Step (d) above, in THF is added 2 mol equivalents of a non-nucleophilic base such as one of those described above in Example 17, followed by 1 mol equivalent of phosgene or 0.33 mol equivalents of triphosgene, and the mixture is stirred. After stirring for from 1 minute to about 1 hour, 5-chlorothiophen-2-ylmethyl alcohol is added, and the mixture is stirred. Reaction progress may be followed by TLC or HPLC. When a sufficient amount of the desired product is formed, the reaction is partitioned between ethyl acetate and water. The organic layer is washed with 0.01 M sodium bicarbonate, water, brine, and dried over sodium sulfate. The mixture is rotary evaporated to give (E)-5-(2,2-difluoro-hex-5-ynoyloxymethylene)-2,4-dioxo-thiazolidine-3-carboxylic acid 5-chloro-thiophen-2-ylmethyl ester, which may be purified, if needed or desired, by chromatography on silica gel or crystallization.

Provenance & Evidence