反应详情

温度

0 °C

To a solution of 0.103 g (0.156 mmol) (3R,4R)-3-[1-(2-amino-ethyl)-1,2,3,4-tetrahydro -quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester [example 15(b)] in 2 ml of tetrahydrofuran was added a solution of 0.101 g (1.56 mmol, 10.0 equiv.) of sodium cyanate in 1 ml of water. The resulting suspension was cooled to 0° C. and 0.156 ml (0.156 mmol, 1.0 equiv.) of 1 N HCl solution was added dropwise. The reaction flask was stoppered and the suspension was stirred for 2 h at 25° C. The reaction mixture was poured into 50 ml of an ice/water mixture, the pH was adjusted to 8 by addition of saturated sodium bicarbonate solution, and the aqueous phase was extracted three times with 50 ml of ethyl acetate. The combined organic phases were washed twice with 25 ml of water, evaporated under reduced pressure and dried in a high vacuum. The thus obtained crude product was purified by chromatography on silica gel using a 100:10:1 v/v/v mixture of dichloromethane/methanol/28% ammonium hydroxide solution as eluent to yield 0.106 g (0.133 mmol, 85.3% of theory) of (3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-[1-(2-ureido-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester as a yellow oil; MS: 799 (M+H)+.

1. extractionthe aqueous phase was extracted three times with 50 ml of ethyl acetate
2. washThe combined organic phases were washed twice with 25 ml of water
3. customevaporated under reduced pressure
4. customdried in a high vacuum
5. customThe thus obtained crude product
6. customwas purified by chromatography on silica gel using
7. additiona 100:10:1 v/v/v mixture of dichloromethane/methanol/28% ammonium hydroxide solution as eluent