Cesium carbonate → (S)-2-sec-Butylamino-6-difluoromethyl-isonicotinic acid methyl ester

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Reaction Steps

Dissolve 2-chloro-6-difluoromethyl-isonicotinic acid methyl ester (200 mg, 0.9 mmol), palladium (II) acetate (20.0 mg, 0.09 mmol), racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (56 mg, 0.09 mmol) and cesium carbonate (438 mg, 1.35 mmol) in toluene (3 mL) in a previously degassed sealed vessel. Flush the mixture with nitrogen gas. Add (S)-(+)-sec-butylamine (0.108 mL, 1.08 mmol) to the solution under nitrogen and heat the sealed mixture overnight at 100° C. Cool the reaction to room temperature. Dilute with diethyl ether and filter through a filtering agent. Concentrate the filtrate and purify (silica gel chromatography, eluting with 10:90 acetate:hexanes) to give the title compound as an oil (60%).

Provenance & Evidence