反应详情

A solution of 2,6-difluoro-N-(1-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide (for a preparation see Example 29)(61.25 g, 153 mmol), chloromethyl bis(1,1-dimethylethyl) phosphate (for a preparation see Intermediate 60)(47.6 g, 184 mmol) and potassium hydroxide (14.18 g, 215 mmol) in N,N-dimethylformamide (500 ml) was stirred at ambient temperature for 7 days. The reaction mixture was partitioned between ethyl acetate (350 ml) and water/brine (250 ml, 1:1 volume/volume). The organic phase was washed with brine (250 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The sample was loaded in dichloromethane and purified on a silica Redisep cartridge 1500 g using a gradient of 0-75% ethyl acetate-cyclohexane over 8 column volumes. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a colourless gum (which started to crystallise to a white solid (72.44 g); LCMS: (System 8) MH+=622, tRET=3.40 min.

1. customThe reaction mixture was partitioned between ethyl acetate (350 ml) and water/brine (250 ml, 1:1 volume/volume)
2. washThe organic phase was washed with brine (250 ml)
3. dry with materialdried over magnesium sulphate
4. customThe solvent was removed in vacuo
5. custompurified on a silica Redisep cartridge 1500 g
6. customevaporated in vacuo