4-Nitrobenzenesulfonyl chloride → cis-Tert-butyl 4-fluoro-5-(4-nitrophenylsulfonyloxy)azepane-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

cis-tert-butyl 4-fluoro-5-hydroxyazepane-1-carboxylate (22.3 g, 95.59 mmol) was dissolved in CH2Cl2 (240 mL). The solution was cooled to 0° C., 4-nitrobenzene-1-sulfonyl chloride (25.42 g, 114.7 mmol) was added and the mixture was stirred for 30 minutes. NEt3 (19.99 mL, 143.4 mmol) was added and the mixture was slowly warmed to ambient temperature over 2 hours and stirred overnight. The mixture was diluted with CH2Cl2 and washed with 1N KHSO4 (2×100 mL) followed by washing with saturated aqueous NaHCO3 (100 mL) and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The crude orange solid was dissolved in minimal hot CH2Cl2 and hexanes were added with stirring until the solution became persistently cloudy. The warm mixture was cooled to ambient temperature and allowed to stand undisturbed for 1 hour. The solids were collected by filtration and the solid was successively washed with hexanes followed by 50% Et2O/hexanes and finally with hexanes again to provide the clean cis isomer of the product as a pale yellow solid (27.05 g, 68%).

Provenance & Evidence