反应详情

A stirred mixture of 2,5-difluoro-4-methyl-N-(methylsulfonyl)benzamide (Preparation 244, 5.07 g, 20.3 mmol), N-bromosuccinimide (freshly recrystallised and dried, 4.71 g, 26.4 mmol) and azobisisobutyronitrile (0.05 g, 0.30 mmol) in 1,2-dichloroethane (100 mL) was heated at reflux under nitrogen whilst being irradiated with light from a lamp. After 2 hours, additional azobisisobutyronitrile (0.05 g, 0.30 mmol) was added and the reaction heated under reflux for 2 hours more. The reaction mixture was cooled to room temperature and evaporated in vacuo. The resulting residue was partitioned between brine (200 mL) and EtOAc (2×150 mL). The combine organic extracts were dried over magnesium sulphate and concentrated in vacuo to yield a pale yellow oil which solidified on standing (7.88 g). The solid was purified by silica gel chromatography eluting with 0 to 30% EtOAc in heptane to afford the title compound as a white solid (3.71 g, 56%):

1. customfreshly recrystallised
2. customdried
3. temperatureat reflux under nitrogen
4. customwhilst being irradiated with light from a lamp
5. temperaturethe reaction heated
6. temperatureunder reflux for 2 hours more
7. customevaporated in vacuo
8. customThe resulting residue was partitioned between brine (200 mL) and EtOAc (2×150 mL)
9. dry with materialThe combine organic extracts were dried over magnesium sulphate
10. concentrationconcentrated in vacuo
11. customto yield a pale yellow oil which
12. customThe solid was purified by silica gel chromatography
13. washeluting with 0 to 30% EtOAc in heptane