Lithium Hexamethyldisilazide → tert-Butyl 1,3-thiazol-4-yl[(2,4,5-trifluorophenyl)sulfonyl]carbamate

Participants

Reaction Steps

To a solution of tert-butyl 1,3-thiazol-4-ylcarbamate (Preparation 3, 28.94 g, 145 mmol) in anhydrous tetrahydrofuran (600 mL) at −70° C., under an atmosphere of nitrogen was added lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1 M in tetrahydrofuran, 145 mL, 145 mmol) drop-wise. The reaction mixture was allowed to warm to ambient temperature and stirred for 1 hour before cooling to −70° C. once again. A solution of 2, 4,5-trifluoro benzenesulfonyl chloride (40 g, 173 mmol) in tetrahydrofuran (80 mL) was added drop-wise and then the reaction mixture was slowly warmed to ambient temperature and stirred for 2 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride solution before concentrating in vacuo. The crude residue was purified by silica gel column chromatography (0% to 15% ethyl acetate in hexanes gradient elution) to afford the title compound as white solid (37 g, 64%).

Provenance & Evidence