Sodium Hydroxide → 3-{1-[2-(5-Methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]piperidin-4-yl}-benzoic acid

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Reaction Steps

To a solution of 3-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-benzoic acid ethyl ester (4.35 g, 10.27 mmol) in methanol (50 mL) was added aq. solution of sodium hydroxide (2 M, 7.7 mL, 15.41 mmol) at RT. After stirring 4 h at RT, the solvent was removed, and the residue was dissolved in THF (30 mL), and aq. solution of lithium hydroxide (121 mg in 5 mL of water) was added at RT. After stirring overnight at RT, the solvent was removed and the residue was dissolved in ethylacetate (50 mL) and the reaction mixture was acidified with 2M aq. solution of HCl until pH 1-2. After separation of phases, the aq. layer was re-extracted with ethylacetate (20 mL), and the combined organic layers were washed with brine (50 mL), dried over sodium sulfate, filtered, and evaporated under reduce pressure to give 3-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-benzoic acid (2.40 g, 59%), which can be used in the next step without further purification. 1H-NMR (400 MHz, d6-DMSO): δ=1.45-1.55 (m, 1H), 1.65-1.1.79 (m, 1H), 1.80-1.91 (m, 2H), 2.22 (s, 3H), 2.67-2.78 (m, 1H), 2.89-2.95 (m, 1H), 3.17-3.24 (m, 1H), 3.95-4.04 (m, 1H), 4.46-4.52 (m, 1H), 5.21-5.38 (dd, 2H, diastereotopic), 6.50 (s, 1H), 7.47 (t, 1H), 7.55 (d, 1H), 7.80 (s, 1H), 7.81 (d, 1H). MS: m/z=396 (M+1).

Provenance & Evidence