反应详情

温度

60 °C

A suspension of crude ethyl 6-[3-endo-({[2-methyl-3-methyloxy)phenyl]carbonyl}amino)-8-azabicyclo[3.2.1]oct-8-yl]pyridine-3-carboxylate (4.72 g, max. 9.55 mmol) and potassium hydroxide (1.07 g, 19.10 mmol) in methanol (90 mL) and water (30 mL) was stirred at 60° C. for 2 hours. After cooling to room temperature, some of the methanol was evaporated, water was added to the resulting mixture, and the pH adjusted to 5 with 1N aqueous hydrochloric acid. The precipitate was filtered, washed with water, and dried to afford 6-[3-endo-({[2-methyl-3-methyloxy)phenyl]carbonyl}amino)-8-azabicyclo[3.2.1]oct-8-yl]pyridine-3-carboxylic acid (3.14 g, 83% yield over two steps). 1H NMR (400 MHz, DMSO-d6): 12.45 (s, 1H), 6.83 (br s, 1H), 8.64 (d, 1H), 8.24 (d, 1H), 7.91 (dd, 1H), 7.23 (t, 1H), 7.02 (d, 1H), 6.86 (d, 1H), 6.75 (d, 1H), 4.60 (br s, 2H), 3.86 (m, 1H), 3.80 (s, 3H), 2.21 (m, 2H), 2.14 (s, 3H), 2.07 (m, 2H), 1.97 (m, 2H), 1.87 (d, 2H); MS (EI) for C22H25N3O4: 396 (MH+).

1. temperatureAfter cooling to room temperature
2. customsome of the methanol was evaporated
3. additionwater was added to the resulting mixture
4. filtrationThe precipitate was filtered
5. washwashed with water
6. customdried