Thionyl Chloride → N-(4'-chloro-2'-fluoro-5'-isopropyloxyphenyl)-5-chloro-3-(trifluoromethyl)pentanamide

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(4'-chloro-2'-fluoro-5'-isopropyloxyphenyl)-5-hydroxy-3-(trifluoromethyl)pentanamide (1.2 g, 3.2 mmol) (Compound 45) in methylene chloride (100 ml), was added thionyl chloride (0.24 ml) in one portion via pipette. The solution turned brown. The reaction mixture was heated to 40°-50° C. for 7 hours, kept at room temperature for 64 hours, heated to 40° C. for 3 hours, and then stirred at room temperature for 18 hours. Then additional thionyl chloride (0.1 ml) was added and the reaction mixture was heated to 40° C. for 4 more hours. After cooling, the solvent was removed in vacuo and the resulting golden brown, semi-solid product mixture was purified via flash chromatography (20 ml fractions, 2'×7' column, 1:9 ethyl acetate/hexanes) to yield a brown solid, m.p. of 57°-63° C.

Provenance & Evidence