3-Fluorobenzaldehyde → HCID 58610198, compound

Participants

Reaction Conditions

Reaction Steps

A solution of lithium diisopropylamide (2M in heptane, 16.9 ml) was added dropwise over 15 min to a stirred solution of 4-benzyl-morpholin-3-one (5.0 g, 26 mmol) and 3-fluorobenzaldehyde (3.55 g, 28.6 mmol) in dried tetrahydrofuran (60 ml) cooled to −70° C. under nitrogen atmosphere. After 1 h at −70° C., the reaction mixture was quenched with aqueous ammonium chloride (100 ml) and extracted with ethyl acetate (100 ml). The extracts were washed with 2M aqueous hydrochloric acid (2×50 ml), brine solution (100 ml) and dried over sodium sulphate. After filtration, the solution was evaporated and the residual oil purified by chromatography on silica eluting with ethyl acetate:hexane 70:30 then ethyl acetate to give diastereomer 1 (2R)-2-[(S)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one and (2S)-2-[(R)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one as a solid (3.8 g) followed by diastereomer 2 (2R)-2-[(R)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one and (2S)-2-[(S)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one as an oil (2.13 g). Diastereomer 1 was recrystallised from ethyl acetate (25 ml) n-hexane (100 ml) to give white needles (2.62 g, 32%).

Provenance & Evidence