反应详情

温度

80 °C

In a sealed tube a mixture of (+)-1-benzyl-3-(2,3-difluorophenyl)pyrrolidin-3-ol (0.40 g, 1.38 mmol), dimethyl formamide (3 mL) and iodopropane (1.35 mL, 13.8 mmol) was heated under microwave irradiation at 80° C. for 45 minutes. The resulting mixture was evaporated, morpholine (2 mL) was added and the mixture was heated under micro-wave irradiation at 130° C. for 30 minutes. Aqueous sodium carbonate (10%, 50 mL) was added and the aqueous phase was extracted with ethyl acetate (2×50 mL), the combined organic phase was washed with aqueous LiCl (5%, 50 mL), dried (Na2SO4) and evaporated. Purification by HPLC on Waters OBD C18, 5 μm (MeOH/33 mM NH3, 40:60 to 60:40) gave the title compound (0.115 g). [α]D=+22.8° (methanol). The amine was converted to the fumaric acid salt and recrystallized from methanol/diethyl ether/diisopropyl ether: M.p. 95-98° C.; MS m/z (relative intensity, 70 eV) 241 (M+, 8), 212, (bp), 182 (41), 84 (88), 57 (24).

1. customThe resulting mixture was evaporated
2. additionmorpholine (2 mL) was added
3. temperaturethe mixture was heated under micro-wave irradiation at 130° C. for 30 minutes
4. additionAqueous sodium carbonate (10%, 50 mL) was added
5. extractionthe aqueous phase was extracted with ethyl acetate (2×50 mL)
6. washthe combined organic phase was washed with aqueous LiCl (5%, 50 mL)
7. dry with materialdried (Na2SO4)
8. customevaporated
9. customPurification by HPLC on Waters OBD C18, 5 μm (MeOH/33 mM NH3, 40:60 to 60:40)