反应详情

A solution of 0.55 g methyl 4-({5-cyclohexyl-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-1-yl}methyl)benzoate from Step C Example 1 in 16 mL ethanol and 6 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 7.95˜7.97 (m, 2H), 7.84˜7.87 (m, 2H), 7.28 (d, J=8.1 Hz, 2H), 7.19 (d, J=8.2 Hz, 2H), 6.56 (s, 1H), 5.48 (s, 2H), 2.60 (tt, J=3.0 & 11.8 Hz, 1H), 1.72˜1.78 (m, 4H), 1.68˜1.72 (m, 1H), 1.37˜1.44 (m, 2H), 1.23˜1.35 (m, 3H).

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