反应详情

Sodium hydroxide (1M; 6.53 mL, 6.53 mmol) was added to a solution of ethyl N-{2-[(cyclopropylmethyl)amino]-1-phenylethyl}-beta-alaninate (1.81 g, 6.22 mmol) in methanol (10 mL). After 1 h, the mixture was concentrated and azeotroped with toluene (3×) to give the crude acid. Diphenylphosphoryl azide (2.68 ml, 12.43 mmol) was added to a solution of the crude acid (1.77 g, 6.22 mmol) and 4-methylmorpholine (1.37 mL, 12.4 mmol) in N,N-dimethylformamide (124 mL). After 18 h, the reaction was concentrated and diluted with water. The mixture was extracted with dichloromethane (3×), and the combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. Purification by silica gel chromatography [100% dichloromethane→90% dichloromethane/10% (10% ammonium hydroxide/methanol)] gave the title compound (1.38 g). MS 245 (M+1). 1H NMR (500 MHz, CDCl3) □ 7.47-7.30 (m, 5H), 3.89-3.88 (m, 2H), 3.65 (dd, J=13.9, 6.6 Hz, 1H), 3.31-3.26 (m, 1H), 3.24-3.21 (m, 1H), 3.02-2.93 (m, 3H), 2.70-2.65 (m, 1H), 1.02-0.97 (m, 1H), 0.58-0.49 (m, 2H), 0.28-0.21 (m, 2H).

1. concentrationthe mixture was concentrated
2. customazeotroped with toluene (3×)
3. customto give the crude acid
4. waitAfter 18 h
5. concentrationthe reaction was concentrated
6. additiondiluted with water
7. extractionThe mixture was extracted with dichloromethane (3×)
8. dry with materialthe combined organic extracts were dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customPurification by silica gel chromatography [100% dichloromethane→90% dichloromethane/10% (10% ammonium hydroxide/methanol)]