Ethyl Acetate → 3-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propionic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of ethyl acetate (2.24 ml, 22.8 mmol) in tetrahydrofuran (6 ml) was added to a −78° C. cold solution of LDA (2 M solution in tetrahydrofuran/n-heptane; 9.8 ml, 19.6 mmol) in tetrahydrofuran (15 ml) within 30 min under an argon atmosphere. The solution was stirred for 30 min at −78° C. and DMPU (3.9 ml, 32.6 mmol) was added within 20 min. A solution of 5-iodomethyl-4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole (2.5 g, 6.5 mmol) in tetrahydrofuran (15 ml) was added within 30 min and stirring was continued for additional 30 min. The mixture was naturally warmed to ambient temperature, stirred for one hour and poured onto aqueous ammonium chloride/ice water 1/1. Twofold extraction with ethyl acetate was followed by washing of the combined extracts with ice water/brine 1/1 (two times), drying over sodium sulfate and removal of the solvent under reduced pressure. The residue was purified by column chromatography (silica gel, heptane/AcOEt) and crystallized from heptane/dichloro-methane to yield 480 mg (1.4 mmol, 21%) of the title compound as light yellow solid.

Provenance & Evidence