4-Methylmorpholine → HCID 118092700, compound

Participants

Reaction Steps

To 16E (8.0 g, 22.91 mmol), 4-methylmorpholine (3.02 mL, 27.5 mmol) in THF (100 mL) at −20° C. was added ethyl chloroformate (2.420 mL, 25.2 mmol). The mixture was stirred for 20 min. The cloudy reaction mixture was filtered. The filtrate was treated with sodium borohydride (1.213 g, 32.1 mmol) and MeOH (30 mL) slowly from −20° C. The mixture was stirred at −20° C. for 15 min. and then at rt for 1 h. The reaction was quenched with addition of sat. ammonium chloride. Organic solvent was removed under reduced pressure. The residue was partitioned between EtOAc/water. The organic layers were collected, washed with sat. sodium bicarbonate and brine, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography (0-40% ethyl acetate/hexanes). The desired fractions were combined and concentrated to give 16F (5.93 g, 17.69 mmol, 77% yield). MS (ESI) (m/z): 357, 359.4 (M+Na)+. 1H NMR (400 MHz, chloroform-d) δ ppm 7.27-7.40 (m, 7H) 7.01 (d, J=8.34 Hz, 1H) 4.56 (s, 2H) 3.92-4.04 (m, 1H) 3.67-3.89 (m, 3H) 3.35-3.49 (m, 1H) 2.34 (s, 3H).

Provenance & Evidence