反应详情

A solution of (R)-1-(2-amino-5-bromo-pyridin-3-ylmethyl)pyrrolidine-2-carboxylic acid methyl ester (6.52 g, 20.8 mmol) in DMSO (200 mL) was treated with NaH (60% dispersion in mineral oil, 0.83 g, 20.7 mmol). After stirring at room temperature for 3 h, the mixture was stored in the freezer for 3 d. The mixture was allowed to warm to room temperature, diluted with H2O (400 mL), and extracted with EtOAc (4×200 mL). The combined organic layers were washed with H2O (3×100 mL) and brine (100 mL), dried over Na2SO4, filtered and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2,/MeOH, 99:1) gave the title compound (3.94 g, 67%) as an off-white solid: MS (ESI) m/e 282 (M+H)+.

1. waitthe mixture was stored in the freezer for 3 d
2. temperatureto warm to room temperature
3. extractionextracted with EtOAc (4×200 mL)
4. washThe combined organic layers were washed with H2O (3×100 mL) and brine (100 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customthe solvent was removed in vacuo
8. customPurification by flash column chromatography (silica gel, CH2Cl2,/MeOH, 99:1)