Lithium hydroxide, monohydrate → 5-(3-Fluoro-phenyl)-3-[(2-hydroxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-thiophene-2-carboxylic acid

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Reaction Steps

3-[(2-Acetoxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-5-(3-fluoro-phenyl)-thiophene-2-carboxylic acid methyl ester (30 mg, 0.063 mmol) was taken in a mixture of THF:MeOH:H2O (3:2:1, 2 mL) and then added 1N aqueous solution of LiOH.H2O (0.38 mL, 0.380 mmol). The reaction mixture was stirred at room temperature for 12 h. Solvents were removed and the residue was partitioned between water and ethyl acetate. The aqueous layer was acidified using 10% KHSO4 solution. The organic layer was separated, dried (Na2SO4) and concentrated. The residue was purified by silica gel column chromatography using chloroform and methanol (8:2) to obtain 5-(3-fluoro-phenyl)-3-[(2-hydroxy-4-methyl-cyclohexanecarbonyl)-isopropyl-amino]-thiophene-2-carboxylic acid (Compound 44) (15 mg, 58%) as a white solid with two rotamers. 1H NMR (CDCl3, 400 MHz): δ7.50-7.25 (m, 3H), 7.06 (m, 2H), 6.25 (bs, 1H), 5.25 (s, 1H, minor), 4.87 (s, 1H, major), 4.13 (s, 1H, major), 3.87 (s, 1H, minor), 2.38-0.45 (m, 17H). ESI− (M-H): 418.

Provenance & Evidence