Chloroacetyl chloride → (6S)-4-benzyl-6-(4-fluorophenyl)morpholin-3-one

Participants

Reaction Conditions

Reaction Steps

To a suspension of (1S)-1-(4-fluorophenyl)-2-(benzylamino)ethanol (22.0 g, 89.69 mmol) in toluene (100 mL) was added dropwise over 1 hr a solution of chloroacetyl chloride (9.3 mL, 116.6 mmol) in toluene (30 mL) at 5-15° C. After stirring for 2 hrs, a solution of triethylamine (17.4 mL, 123.7 mmol) in toluene (20 mL) was added dropwise over 15 min to the mixture at 10-15° C. The mixture was stirred for 17 hrs at room temperature. After HPLC analysis to confirm a disappearance of the aminoethanol, the mixture was cooled to 2° C., and sodium methoxide (52 g, 269.07 mmol, 28% methanol solution) was added dropwise over 15 min. The mixture was stirred at 2-5° C. for 9 hrs, and water (60 mL) was added. The organic layer was separated and washed successively with 0.5N hydrochloric acid and saturated aqueous sodium hydrogencarbonate solution. The solvent was evaporated under reduced pressure to give (6S)-6-(4-fluorophenyl)-4-(benzyl)morpholin-3-one (27.78 g) as a yellow oil.

Provenance & Evidence