(3S)-4-Benzyl-3-(4-fluorophenyl)morpholin-2-one → (2R,3S)-4-Benzyl-3-(4-fluorophenyl)-2-hydroxy-2-(prop-2-enyl)morpholine

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Reaction Steps

(3S)-4-Benzyl-3-(4-fluorophenyl)-2-morpholinone (see International Patent Specification No. WO 95/18124) (13.6 g, 47.6 mmol) was dissolved in anhydrous tetrahydrofuran (200 ml) and cooled to below -70° C. under an inert atmosphere. Allyl magnesium chloride (26.2 ml of a 2.0M solution in tetrahydrofuran; 52.4 mmol) was added dropwise over 15 minutes, maintaining the temperature below -70° C. After 30 minutes, the reaction was quenched by the addition of a saturated solution of ammonium chloride and allowed to warm to room temperature. The resulting suspension was extracted with ethyl acetate (3×100 ml), and the combined organic extracts dried (MgSO4) and concentrated in vacuo to yield the title compound in ~3:1 mixture of the lactols as a light yellow oil (15.3 g, 98%), which was used without further purification. m/z (ES+) 328 (M+1, 22%), 310 (M--OH, 61), 269 (100).

Provenance & Evidence