反应详情

A flask was charged with the product from Step A (2.80 g, 17.5 mmol), benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (9.28 g, 21.0 mmol) and dry DMF (35 mL). The suspension was stirred at ambient temperature for 2 minutes and (R)-2-(2,5-difluorophenyl)pyrrolidine (Preparation A, 3.84 g, 21.0 mmol) and diisopropylethylamine (6.78 g, 62.5 mmol) were sequentially added (mild exotherm). The mixture was stirred at ambient temperature for 3 hours and poured into H2O (175 mL). The mixture was extracted with 50% EtOAc-hexanes and the combined organic fractions were washed sequentially with 1M HCl, H2O, 1M Na2CO3 and saturated NaCl. The solution was dried over MgSO4/activated carbon and filtered through a short SiO2 plug (350 mL course frit funnel, ¼ full of SiO2, capped with a layer of MgSO4) using 50% EtOAc-hexanes for elution. The solution was concentrated to give the title compound as a brittle white foam that was crushed to a flowing white solid and dried in vacuum (5.50 g, 97%). MS (apci) m/z=326.2 (M+H).

1. stirringThe mixture was stirred at ambient temperature for 3 hours
2. extractionThe mixture was extracted with 50% EtOAc-hexanes
3. washthe combined organic fractions were washed sequentially with 1M HCl, H2O, 1M Na2CO3 and saturated NaCl
4. dry with materialThe solution was dried over MgSO4/activated carbon
5. filtrationfiltered through a short SiO2 plug (350 mL course frit funnel
6. customfull of SiO2, capped with a layer of MgSO4)
7. washfor elution
8. concentrationThe solution was concentrated