反应详情

温度

40 °C

To a solution of (5R)-5-phenylmorpholin-3-one 5 (2.500 g, 14.11 mmol) in THF (57.02 mL) cooled in an ice bath was added lithium aluminium hydride (2M in THF) (9.170 mL of 2 M, 18.34 mmol) slowly over 5 mins. On complete addition mixture was warmed to 40° C. and stirred for 1 h. The reaction mixture was cooled down to rt then added more LAH (4.9 mL, 0.7 eq) and warmed back to 40° C. for a further 1 h. The reaction mixture was cooled in an ice bath and EtOAc (5 ml) was slowly added and the resulting mixture stirred at rt for 30 mins and then added very small amount of water until no vigorous reaction occurred. The reaction mixture turns thick so methanol (approx 50 mL) was added followed by a small amount of 1M NaOH to make mixture basic, filtered through celite, washing through with methanol. The filtrate was concentrated in vacuo and then loaded onto SCX2 (50 g) washed with methanol and filtrate discarded. The product was then eluted with 2M ammonia in methanol and the filtrate concentrated in vacuo to leave product as an orange oil that solidified on standing; 1H NMR (400.0 MHz, DMSO) d 2.85 (2H, m), 3.14 (1H, m), 3.45 (1H, m), 3.66 (1H, m), 3.78 (3H, m), 7.23 (1H, m) 7.31 (2H, m) and 7.41 (2H, m) ppm; MS (ES+) 164.1

1. temperatureThe reaction mixture was cooled down to rt
2. temperaturewarmed back to 40° C. for a further 1 h
3. temperatureThe reaction mixture was cooled in an ice bath
4. stirringthe resulting mixture stirred at rt for 30 mins
5. customuntil no vigorous reaction
6. additionwas added
7. filtrationfiltered through celite
8. washwashing through with methanol
9. concentrationThe filtrate was concentrated in vacuo
10. washwashed with methanol and filtrate
11. washThe product was then eluted with 2M ammonia in methanol
12. concentrationthe filtrate concentrated in vacuo
13. customto leave product as an orange oil that solidified