Triethylamine → N-[(1R,2S)-2-hydroxycyclohexyl]-2-[3-(methylsulfanyl)phenoxy]nicotinamide

Participants

Reaction Steps

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (294 mg, 1.53 mmol) was added to a solution of 2-(3-methylsulfanyl-phenoxy)-nicotinic acid (200 mg, 0.765 mmol), (1S,2R)-2-aminocyclohexanol hydroformate [8151/194/1] (128 mg, 0.765 mmol), 1-hydroxybenzotriazole (114 mg, 0.842 mmol) and triethylamine (430□l, 3.10 mmol) in dimethylformamide (5 ml) under nitrogen at room temperature. The reaction was stirred for 18 h and partitioned between diethyl ether (25 ml) and water (25 ml). The organic phase was washed with brine (30 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of ethyl acetate: cyclohexane (35:65 to 50:50) to give an off-white solid which was purified by flash column chromatography using ethyl acetate:cyclohexane (50:50 as eluant) to give N-[(1R,2S)-2-hydroxycyclohexyl]-2-[3-(methylsulfanyl)phenoxy]nicotinamide (133 mg) as a gum.

Provenance & Evidence