Hydrochloric Acid → Ethyl 3-methyl-6-(trifluoromethyl)thieno[3,2-b]pyridine-2-carboxylate

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Reaction Steps

To a solution (50 mL) of 3-chloro-5-(trifluoromethyl)pyridine-2-carbonitrile (5.00 g) in tetrahydrofuran was added 3.0M solution (16.1 mL) of methylmagnesium bromide in diethyl ether at 0° C., and the mixture was stirred for 3 hr under argon atmosphere. To the reaction mixture was added 1N hydrochloric acid (300 mL) to acidify the solution to pH=3-4, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0-10% ethyl acetate/hexane) to give a pale-yellow solid. To a mixture of the obtained solid, ethyl mercaptoacetate (1.61 mL) and N,N-dimethylformamide (30 mL) was added potassium carbonate (5.56 g), and the mixture was stirred at 50° C. for 10 hr. Water was added to quench the reaction, and the precipitated solid was collected by filtration to give the title object compound (3.76 g, 54%) as a white solid.

Provenance & Evidence