反应详情

温度

60 °C

Aqueous 1N sodium hydroxide solution (1.2 mL, 1.2 mmol) was added to a solution of methyl (R)-3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)-5-methylbenzoate (123 mg, 0.24 mmol) in THF (5 mL). The reaction mixture was heated to 60° C. for 48 hours, and then the volatiles were evaporated under reduced pressure. The remaining aqueous phase was washed with diethyl ether (10 mL). The aqueous phase was then adjusted to pH 3 with aqueous 1N HCl (1 mL), and then was extracted with EtOAc (2 times with 10 mL). The combined organic phases were washed with brine (2 times with 10 mL), dried over MgSO4, filtered, and concentrated to provide (R)-3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)-5-methylbenzoic acid (84.4 mg, 60%). 1H NMR (500 MHz, CDCl3) δ 8.77 (br s, 2H), 7.84 (s, 1H), 7.81 (s, 1H), 7.41 (s, 1H), 7.00 (d, 1H), 6.95 (m, 1H), 6.87 (m, 2H), 6.48 (br s, 1H), 4.65 (d, 2H), 4.42 (m, 1H), 4.27 (m, 1H), 4.13 (m, 1H), 4.00 (m, 2H), 3.85 (m, 1H), 3.71 (m, 1H), 2.40 (s, 3H), 2.11 (m, 1H), 1.97 (m, 2H), 1.60 (m, 1H), 1.38 (t, 3H). MS (ES+) 491.1 (M+H).

1. customthe volatiles were evaporated under reduced pressure
2. washThe remaining aqueous phase was washed with diethyl ether (10 mL)
3. extractionwas extracted with EtOAc (2 times with 10 mL)
4. washThe combined organic phases were washed with brine (2 times with 10 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated