反应详情

To a slurry of NaH (60% dispersion in oil, 5.9 g, 148.5 mmol, 3.0 eq.) in DMP (40 mL) at 65° C. under N2 was added a solution of N-boc-4-hydroxy piperidine (10 g, 49.5 mmol, 1.0 eq.) in DMF (50 mL). After stirring for about 2 hours, a solution of 1-bromo-2-fluoro benzene (11.0 mL, 99.0 mmol, 2.0 eq.) in DMF (10 mL) was added dropwise. The resulting mixture was stirred at 65° C. overnight. The mixture was diluted with EtOAc (250 mL) and washed with water (100 mL) and brine (100 mL). The aqueous layer was extracted with EtOAc (3×). The combined organic extracts were dried (Na2SO4), filtered and concentrated. Purification by flash chromatography (250 g SiO2, linear gradient, 40 mL/min, 0% to 30% EtOAc/Hexane over 20 minutes and 30% EtOAc for 13 minutes) afforded title compound (14.2 g, 39.8 mmol, 81%). LRMS (electrospray): 358.0.

1. stirringThe resulting mixture was stirred at 65° C. overnight
2. washwashed with water (100 mL) and brine (100 mL)
3. extractionThe aqueous layer was extracted with EtOAc (3×)
4. dry with materialThe combined organic extracts were dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification by flash chromatography (250 g SiO2, linear gradient, 40 mL/min, 0% to 30% EtOAc/Hexane over 20 minutes and 30% EtOAc for 13 minutes)