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

Temperature

0 °C

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%).

1. temperaturethe mixture was slowly warmed to ambient temperature over 2 hours
2. stirringstirred overnight
3. washwashed with 1N KHSO4 (2×100 mL)
4. washby washing with saturated aqueous NaHCO3 (100 mL) and brine
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe crude orange solid was dissolved in minimal hot CH2Cl2
9. additionhexanes were added
10. stirringwith stirring until the solution
11. temperatureThe warm mixture was cooled to ambient temperature
12. waitto stand undisturbed for 1 hour
13. filtrationThe solids were collected by filtration
14. washthe solid was successively washed with hexanes

ORD record

ord-e40ae3662848473b83f6476f5e054d54

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08575145B2