反应详情

温度

0 °C

A slurry of benzyl (2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate (1:1) (100 g, 232 mmol) in ethanol (2000 ml) was cooled to 0° C. A solution of sodium ethoxide in ethanol (216 ml, 580 mmol, 21 wt % solution) was added slowly and the mixture was stirred for 1 h at 0° C. Acetic acid (13.3 ml, 232 mmol) was added and the mixture was concentrated under vacuum below 35° C. to a final volume of 300 ml. Ethyl acetate (700 ml) was added and the mixture was concentrated to 300 ml. This procedure was repeated twice. Water (1800 ml) was added to the mixture followed by aqueous ammonia (variable) until the pH of the aqueous layer was 7.5 to 8. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×300 ml). The combined organic layers were washed with water (500 ml) and concentrated to a final volume of 300 ml. The solution was filtered and diluted with ethyl acetate (700 ml) and warmed to 35° C. A solution of oxalic acid dihydrate (30 g, 237 mmol) in acetone (200 ml) was added and the mixture was cooled to room temperature. The solids were isolated by filtration, washed with ethyl acetate and dried under vacuum at 35° C. to obtain ethyl (2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate (1:1) as a white solid (80.7 g, 94%).

1. concentrationthe mixture was concentrated under vacuum below 35° C. to a final volume of 300 ml
2. additionEthyl acetate (700 ml) was added
3. concentrationthe mixture was concentrated to 300 ml
4. additionWater (1800 ml) was added to the mixture
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with ethyl acetate (2×300 ml)
7. washThe combined organic layers were washed with water (500 ml)
8. concentrationconcentrated to a final volume of 300 ml
9. filtrationThe solution was filtered
10. additiondiluted with ethyl acetate (700 ml)
11. temperaturewarmed to 35° C
12. temperaturethe mixture was cooled to room temperature
13. customThe solids were isolated by filtration
14. washwashed with ethyl acetate
15. customdried under vacuum at 35° C.