反应详情

A solution of 0.19 g methyl 4-({3-cyclohexyl-5-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-1-yl}methyl)benzoate from Step C Example 1 in 6 mL ethanol and 2.5 mL water was treated with 2.4 equivalents of 5 N NaOH solution till the hydrolysis was complete based on HPLC. After evaporating ethanol under reduced pressure, the residue was acidified with 20% molar excess of 2 N HCl to precipitate the acid product. Extract the reaction mixture with 2×35 mL EtOAc. Wash the combined organic layer with saturated brine, dry over anhydrous Na2SO4, and evaporate to give the title compound as a white solid. It can be recrystallized from 5:3 MeCN and water to give fine crystalline needles. 1H NMR (CDCl3, 500 MHz) δ 7.89 (d, J=8.3 Hz, 2H), 7.39˜7.42 (m, 2H), 7.29 (d, J=8.1 Hz, 2H), 7.00 (d, J=8.3 Hz, 2H), 6.30 (s, 1H), 5.38 (s, 2H), 2.67 (tt, J=3.5 & 11.5 Hz, 1H), 1.97˜2.01 (m, 2H), 1.80˜1.85 (m, 2H), 1.71˜1.75 (m, 1H), 1.38˜1.53 (m, 4H), 1.26˜1.33 (m, 1H). LC-MS: 2.47 min. (M+H=445.3).

1. customAfter evaporating ethanol under reduced pressure
2. customto precipitate the acid product
3. extractionExtract the reaction mixture with 2×35 mL EtOAc
4. washWash the combined organic layer with saturated brine
5. dry with materialdry over anhydrous Na2SO4
6. customevaporate