Ethyl Acetate → (R)-3-phenylmorpholine

Participants

Reaction Conditions

Reaction Steps

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

Provenance & Evidence