Water → 3-[(1-Cyano-piperidin-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid

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Reaction Conditions

Reaction Steps

3-[(1-cyano-piperidin-4-yl)-(4-methyl cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (150 mg, 0.32 mmol) was dissolved in a 4:1 mixture of dioxane: H2O (3.2 ml) and treated with LiOH.H2O (20 mg, 0.48 mmol). After 2 hours of stirring at 50° C., the solvents were removed and then partitioned between 5 ml of H2O acidified to pH 4 and 5 ml of EtOAc. The organic layer was separated and the aqueous phase was washed twice with ethyl acetate (2×5 mL). The combined ethyl acetate layer was dried (Na2SO4) and concentrated. The residue was purified by silica gel column chromatography using (5% MeOH/CH2Cl2) to provide 3-[(1-Cyano-piperidin-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid (114.3 mg, 78% yield) as pale green foam. 1H NMR (DMSO-d6, 400 MHz): 7.80 (m, 2H), 7.45 (m, 4H), 4.44 (m, 1H), 3.35 (m, 2H), 3.13 (m, 2H), 1.96 (t, 1H), 1.88 (d, 1H), 1.75 (m, 1H), 1.70-1.40 (m, 6H), 1.20 (m, 3H), 0.70 (d, 3H), 0.60 (m, 2H).

Provenance & Evidence