反应详情

To a suspension of [4-(5-amino-3-tert-butyl-pyrazol-1-yl)-phenyl]-methanol (WO 2011/070368, which is incorporated herein by reference in its entirety; 3.05 g, 12.4 mmol) in aq. NaOH solution (1M, 31 mL, 31 mmol) and EtOAc (30 mL) at RT was added 2,2,2-trichloroethyl chloroformate (1.88 mL, 13.7 mmol) over 3 min (CARE: exotherm to 35° C.) and the mixture stirred at RT for 1 h. The aqueous layer was extracted with EtOAc (20 mL), then the combined organics washed with brine (25 mL), dried (Na2SO4), filtered and concentrated in vacuo to leave a pale orange solid. Recrystallisation from hot cyclohexane-EtOAc (3:1, 30 mL) and drying in vacuo gave the title compound as a flocculent off-white solid (3.87 g, 74%). LCMS (Method 3): Rt 4.00 min, m/z 420, 422 [MH+].

1. extractionThe aqueous layer was extracted with EtOAc (20 mL)
2. washthe combined organics washed with brine (25 mL)
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customto leave a pale orange solid
7. customRecrystallisation from hot cyclohexane-EtOAc (3:1, 30 mL)
8. customdrying in vacuo