反应详情

温度

90 °C

A mixture of 2-(5-bromo-pyrazin-2-yl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (0.06 g, 0.146 mmol), (2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl (0.045 g, 0.292 mmol), R-(−)-BINAP (0.007 g, 0.011 mmol), and anhydrous toluene (3 mL) was de-gassed and refilled with N2 in three cycles. Pd2(dba)3 (0.0034 g, 0.0037 mmol,), and sodium t-butoxide (0.021 g, 0.212 mmol) was then added to the mixture and de-gassed and refilled with N2 in three additional cycles. The reaction mixture was heated and stirred at 90° C. for 16 hours. The reaction mixture was allowed to cool to room temperature and quenched with water (1 mL). The aqueous phase was extracted with dichloromethane (3×10 mL). The combined organics were washed with sodium bicarbonate (5 mL), and brine (10 mL), dried over Na2SO4, concentrated under vacuum. Purification by column chromatography on silica gel (0-10%) methanol in dichloromethane afforded 0.0257 (37%) of the title compound.

1. customwas de-gassed
2. additionrefilled with N2 in three cycles
3. customde-gassed
4. additionrefilled with N2 in three additional cycles
5. temperatureThe reaction mixture was heated
6. temperatureto cool to room temperature
7. customquenched with water (1 mL)
8. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
9. washThe combined organics were washed with sodium bicarbonate (5 mL), and brine (10 mL)
10. dry with materialdried over Na2SO4
11. concentrationconcentrated under vacuum
12. customPurification by column chromatography on silica gel (0-10%) methanol in dichloromethane