反应详情

1-chloroethyl chloroformate (0.87 ml, 8.09 mmol) was added to an ice-cooled solution of 1-benzhydryl-3-(4-fluorophenoxy)azetidine (D21) (1.8 g, 5.39 mmol) in 1,2 dichloroethane (18 ml) and the resulting mixture was heated under reflux for 3 hours. The reaction mixture was evaporated in vacuo and the residue was re-dissolved in methanol (10 ml). This solution was heated under reflux overnight then cooled at room temperature and evaporated in vacuo. The obtained residue was loaded on SPE-SCX (20 g) cartridge. The ammonia fractions, after evaporation in vacuo, were loaded on by SPE-Si (5 g) cartridge eluting with a mixture dichloromethane/dichloromethane:NH3 (2M solution in MeOH) (from 100/0 to 80/20). Collected fractions after solvent evaporation afforded the title compound (D49) (0.9 g)

1. temperaturethe resulting mixture was heated
2. temperatureunder reflux for 3 hours
3. customThe reaction mixture was evaporated in vacuo
4. dissolutionthe residue was re-dissolved in methanol (10 ml)
5. temperatureThis solution was heated
6. temperatureunder reflux overnight
7. customevaporated in vacuo
8. customThe ammonia fractions, after evaporation in vacuo
9. washeluting with a mixture dichloromethane/dichloromethane
10. customCollected fractions after solvent evaporation