反应详情

温度

60 °C

Add sodium cyanoborohydride (3.6 g, 57.4 mmol) portion wise to a solution of 2-(4-benzyloxy-2,6-dichloro-benzyl)-2-(2-oxo-ethyl)-malonic acid diethyl ester (6.7 g, 14.4 mmol) (Preparation 10) and 4,5,6,7-tetrahydro-3H-benzoimidazol-5-ylamine dihydrochloride salt (6.0 g, 28.7 mmol) (Preparation 1) in 70 ml of Methanol. After 3 h, add 4 ml of acetic acid and warm to 60° C. for 16 h. Most of the Methanol is removed via rotovap. Quench the resulting mixture with saturated bicarbonate and extract with ethyl acetate. Dry extracts over sodium sulfate, concentrate, and purify by normal phase column chromatography (0-10% methanol in ethyl acetate) to afford 3-(4-Benzyloxy-2,6-dichloro-benzyl)-2-oxo-1-(4,5,6,7-tetrahydro-3H-benzoimidazol-5-yl)-pyrrolidine-3-carboxylic acid ethyl ester as a white solid (3 g).

1. customMost of the Methanol is removed via rotovap
2. customQuench the resulting mixture with saturated bicarbonate
3. extractionextract with ethyl acetate
4. customDry
5. concentrationconcentrate
6. custompurify by normal phase column chromatography (0-10% methanol in ethyl acetate)