Ammonium Chloride → HCID 58042307, compound

Participants

Reaction Conditions

Reaction Steps

N-(2,4-Dimethoxybenzyl)-1,3-thiazol-2-yl-amine (Preparation 91, 8.010 g, 0.032 mol) was dissolved in tetrahydrofuran (100 mL) and the solution was cooled to −78° C. Lithium hexamethyldisilazide in tetrahydrofuran (35.2 mL, 1M) was added dropwise to the reaction mixture. The cooling bath was removed and the reaction mixture was allowed to stir for 30 minutes to attain room temperature before re-cooling to −78° C. and a solution of 3-cyano-4-fluorobenzenesulfonyl chloride (7.028 g, 0.032 mol) in tetrahydrofuran (80 mL) was added dropwise to the reaction mixture. The reaction was allowed to stir 30 minutes at −78° C. before pouring it into saturated aqueous ammonium chloride (50 mL). The aqueous phase was separated and extracted with ethyl acetate (3×30 mL). The combined organic phases were washed twice with 10% aqueous citric acid solution (30 mL), water (30 mL), brine (20 mL), dried over MgSO4, filtered and evaporated. The residue was purified by column chromatography (120 g silica gel column, hexanes/ethyl acetate gradient elution 100/0 to 0/100). Product fractions were combined and evaporated. The residue was triturated with 10% tert-butyl methyl ether in hexanes and the resulting off-white solid collected by filtration and rinsed with hexanes and vacuum dried to provide the title compound (3.58 g).

Provenance & Evidence