反应详情

To a solution of 6-bromo-N-methoxy-N-methylpyridine-2-carboxamide (5.29 g, 21.58 mmol) in dry THF (120 mL) at −78° C. (dry ice/acetone bath) under nitrogen was added nBuMgCl (15.2 mL of a 20% wt solution in THF/toluene, 25.84 mmol) drop-wise over 15 minutes. The resulting yellow mixture was stirred at this temperature for 1 hour and was then allowed to warm to 0° C. (ice/water bath) slowly over 1.5 hours and then to rt over 18 hours. The yellow cloudy mixture was then added portion-wise to a stirred solution of aqueous HCl (2M, 200 mL) and the resulting mixture partitioned with EtOAc (200 mL) and the layers separated. The aqueous was re-extracted with EtOAc (200 mL) and the combined organic layer washed with brine (300 mL), dried (MgSO4) filtered and reduced to give a yellow/orange oil. Purification by Biotage™ chromatography (silica) eluting with cyclohexane:EtOAc (gradient 20:1 to 1:2) afforded the title compound (2.51 g).

1. waitto rt over 18 hours
2. customthe resulting mixture partitioned with EtOAc (200 mL)
3. customthe layers separated
4. extractionThe aqueous was re-extracted with EtOAc (200 mL)
5. washthe combined organic layer washed with brine (300 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. customto give a yellow/orange oil
9. customPurification by Biotage™ chromatography (silica)
10. washeluting with cyclohexane