Potassium Carbonate → 2-(4-Methylsulfanyl-phenoxy)-nicotinic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

2-Chloronicotinic acid methyl ester (12 g, 69.9 mmol), 4-methylsulfanylphenol (9.80 g, 69.9 mmol) and potassium carbonate (14.5 g, 0.105 mol) were suspended in dimethylformamide (300 ml) and the reaction was heated to 65° C. and stirred at this temperature under nitrogen for 10 h. It was then heated to 90° C. and stirred at this temperature for 7 h, and then progressed to 100° C. and stirred for 16 h. The reaction was cooled to room temperature, concentrated under reduced pressure and the residue was diluted with water (300 ml). It was then extracted with diether (3×250 ml) and the combined organic extracts were washed with water (2×100 ml), dried over MgSO4 and the solvent removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:concentrated aqueous ammonia (99.5:0.5:0.05, by volume) to give 2-(4-methylsulfanyl-phenoxy)-nicotinic acid methyl ester (8.0 g) as a white solid.

Provenance & Evidence