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

To a solution of tert-butyl 1,3-thiazol-4-ylcarbamate (Preparation 72, 28.94 g, 144.55 mmol) in anhydrous tetrahydrofuran (600 ml), cooled to −70° C., under nitrogen was added lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1 M in tetrahydrofuran, 144.55 ml, 144.55 mmol) dropwise. The reaction mixture was warmed to room temperature and stirred for 1 hour before cooling −70° C. 2,4,5-trifluoro benzenesulfonyl chloride (40 g, 173.46 mmol) in tetrahydrofuran (80 ml) was added dropwise and then the reaction mixture was slowly warmed to room temperature and stirred for 2 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. Organic layer was washed with water and saturated aqueous sodium chloride solution before concentrating in vacuo. The crude residue was purified by column chromatography eluting with ethyl acetate:hexane (gradient 1:19 to 3:17, by volume) to afford the title compound as white solid, 37 g, 64% yield.

1. temperaturebefore cooling −70° C
2. temperaturethe reaction mixture was slowly warmed to room temperature
3. stirringstirred for 2 hours
4. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution
5. extractionextracted with ethyl acetate
6. washOrganic layer was washed with water and saturated aqueous sodium chloride solution
7. concentrationbefore concentrating in vacuo
8. customThe crude residue was purified by column chromatography
9. washeluting with ethyl acetate

ORD record

ord-7306e2eed2f54da08c741f8529c0b3a6

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08907101B2