反应详情

To a solution of (2S,4R)-BOC-4-hydroxyproline methyl ester (126.3 g, 515 mmol) in DMF (960 mL) at 0° C. was added N,N′-carbonyldiimidazole (83.51 g, 515 mmol). The reaction mixture was stirred at RT for 3 hours. 4-Bromoisoindoline hydrochloride (120 g, 515 mmol) and DIPEA (96.3 mL, 540 mmol) were added, and the reaction mixture heated to 50° C. for 6 hours. The reaction mixture was then allowed to cool to RT and stirred overnight. The reaction mixture was partitioned between EtOAc (3 L) and 10% aqueous KHSO4 (6 L), the aqueous re-extracted with EtOAc (2 L) and the combined organic phases washed with 10% aqueous NaHCO3, brine, dried over Na2SO4 and solvent evaporated to a foam (239 g). LRMS (ESI) m/z 471.0 [(M+H)+; calcd for C20H26BrN2O6: 471.1].

1. temperaturethe reaction mixture heated to 50° C. for 6 hours
2. temperatureto cool to RT
3. stirringstirred overnight
4. customThe reaction mixture was partitioned between EtOAc (3 L) and 10% aqueous KHSO4 (6 L)
5. extractionthe aqueous re-extracted with EtOAc (2 L)
6. washthe combined organic phases washed with 10% aqueous NaHCO3, brine
7. dry with materialdried over Na2SO4 and solvent
8. customevaporated to a foam (239 g)