反应详情

To an ice-bath cooled and stirred solution of 5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2,3-difluorobenzonitrile (Intermediate 6, 500 mg, 0.96 mmol) in DMF was added t-BuOK (161 mg, 1.4 mmol) followed by acetohydroxamic acid (108 mg, 1.4 mmol). The mixture was brought to room temperature and stirred for 12 hours. The reaction mixture was diluted with EtOAc and washed successively with 1 N HCl (1×250 mL), water and brine. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was purified over silica gel flash column using a gradient of ethyl acetate in pet. ether to give the title compound as a white solid. Yield: 200 mg, (70%).

1. temperatureTo an ice-bath cooled
2. customwas brought to room temperature
3. washwashed successively with 1 N HCl (1×250 mL), water and brine
4. dry with materialThe organic layer was dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified over silica gel flash column