反应详情

温度

50 °C

To a mixture of 1-(2-pyridyl)cyclopentanecarboxylic acid, benzyl ester-(Step A, 0.20 g, 0.71 mmol) in acetonitrile (3 mL) and water (1.5 mL) was added lithium hydroxide monohydrate (0.24 g, 5.6 mmol). After stirring at room temperature for 5 h and 50° C. overnight, the reaction mixture was concentrated to dryness. The residue was azeotroped with toluene and was suspended in methylene chloride (6 mL) and dimethylformamide (3 mL), and was added N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-amine hydrochloride (Diastereomer α, Reference Example 2, 0.40 g, 0.14 mm), 4-dimethylaminopyridine (0.10 g, 0.71 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (38 mg, 0.19 mmol). After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate (50 mL), washed with water and brine, dried over anhydrous sodium sulfate and concentrated to dryness. N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-1-(2-pyridyl)cyclopentanecarboxamide was obtained by flash column chromatography on silica gel eluted with 15-20% ethyl acetate in hexane. 1H NMR (400 MHz, CD3OD): δ 8.52 (d, 1H), 7.77 (t, 1H), 7.48 (d, 1H), 7.35-7.08 (m, 4H), 7.00 (d, 2H), 6.94 (d, 2H), 6.68 (d, 2H), 4.20 (m, 1H), 2.80 (dd, 1H), 2.73 (m, 1H), 2.60 (m, 2H), 2.45 (m, 1H), 2.30 (m, 1H), 2.18 (m, 1H), 1.85-1.65 (m, 4H), 0.82 (d, 3H). LC-MS: m/e 433 (M+H)+ (3.2 min).

1. concentrationthe reaction mixture was concentrated to dryness
2. customThe residue was azeotroped with toluene
3. stirringAfter stirring at room temperature overnight
4. washwashed with water and brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated to dryness