Lithium → 4-{[(2,4-Dimethoxybenzyl)(1,3-thiazol-2-yl)amino]sulfonyl}-3-fluorobenzoic acid

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Reaction Conditions

Reaction Steps

N-(2,4-dimethoxybenzyl)-1,3-thiazol-2-amine (Preparation 6, 2.34 g, 9.35 mmol, 0.95 eq) was suspended in THF (20 ml) and stirred at 0° C. for 10 minutes. 1,1,1,3,3,3-Hexanemethyldisilazane lithium salt (LiHMDS, 1M in THF, 19.5 ml, 20 mmol, 2.0 eq) was added dropwise maintaining the temperature below 30° C. and the reaction mixture stirred for a further 30 minutes. A solution of 4-(chlorosulfonyl)-3-fluorobenzoic acid (Preparation 9, 2.35 g, 9.85 mmol, 1 eq) in THF (15 ml) was added dropwise maintaining the reaction temperature below 30° C. and the reaction mixture stirred at room temperature for 2 hours. The reaction mixture was diluted with brine (10 ml), extracted into ethyl acetate (10 ml), dried over sodium sulphate, filtered and evaporated in vacuo. The crude material was slurried in t-butylmethyl ether and stirred at room temperature for 72 hours. The resulting solid was collected by filtration to yield the title compound as a beige solid (744 mg, 1.64 mmol, 17%).

Provenance & Evidence