反应详情

To a solution of (5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)(4-chloro-2-methylphenyl)methanol (31.6 g, 91 mmol) in DCM (500 mL) at about 0° C. was added Dess-Martin periodinane (42.3 g, 100 mmol). The cold bath was removed and the mixture was allowed to warm to rt. After about 3 h additional Dess-Martin periodinane (1.92 g, 4.54 mmol) was added and the mixture was stirred for about 30 min. A saturated aqueous NaHCO3 solution (500 mL) was added then the mixture was filtered. The solvent layers of the filtrate were separated. The filter cake was triturated with DCM then filtered. The combined organic layers were washed with brine (500 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was heated in EtOAc (300 mL) to just below the boiling point then filtered. The filtrate was allowed to cool to rt and the precipitate was collected by filtration. Additional crops of desired product were obtained by concentration of the filtrate followed by precipitation with Et2O/heptane. The crops were combined to give (5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)(4-chloro-2-methylphenyl)methanone (23.47 g, 75%): LC-MS (Table 1, Method g) Rt=2.43 min, m/z 346/348 (M+H)+; 1H-NMR (DMSO, Bruker 400 MHz) δ 8.20-8.15 (m, 1H), 7.77-7.67 (m, 2H), 7.33-7.28 (m, 1H), 7.21-7.13 (m, 2H), 7.08-7.01 (m, 1H), 3.96-3.89 (s, 3H), 2.50 (s, 3H).

1. customThe cold bath was removed
2. filtrationthe mixture was filtered
3. customThe solvent layers of the filtrate were separated
4. customThe filter cake was triturated with DCM
5. filtrationthen filtered
6. washThe combined organic layers were washed with brine (500 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. temperatureThe residue was heated in EtOAc (300 mL) to just below the boiling point
11. filtrationthen filtered
12. temperatureto cool to rt
13. filtrationthe precipitate was collected by filtration