反应详情

To an ice cooled and stirred solution of [2-((2R,6S)-2,6-dimethyl-morpholin-4-yl)-3,4-difluoro-phenyl]-methanol (Intermediate 2, 27.0 g, 105 mmol) in CH2Cl2 was added imidazole (8.5 g, 126 mmol) followed by t-butyl chlorodiphenylsilane (30 mL, 115 mmol) over a period of 15 min. The mixture was brought to room temperature and stirred for 12 h during which tlc showed the disappearance of starting material. The reaction mixture diluted with CH2Cl2 and washed successively with 1 N HCl (1×250 mL), water and brine. The organic layer dried (Na2SO4), filtered and concentrated. The residue was purified over a silica gel flash column using a gradient of ethyl acetate in pet. ether to give the title compound as a white solid. Yield: 45 g (94%).

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