3-Morpholinone → (S)-4-Benzyl-2-(4-fluorophenyl)morpholine

To a solution of (6S)-6-(4-fluorophenyl)-4-(benzyl)morpholin-3-one (1.16 g) in tetrahydrofuran (10 mL) was added dropwise over 15 min a solution of sodium bis(2-methoxyethoxy)aluminum hydride (70% in toluene, 3.2 mL, 11.4 mmol) in tetrahydrofuran (5 ml) at 65° C., and the reaction mixture was refluxed over 1.5 hrs. After HPLC analysis to confirm a disappearance of the morpholin-3-one, the reaction was quenched by addition of water (0.6 mL), 15% aqueous sodium hydroxide solution (0.6 mL) and water (1.8 mL) at 0° C. The reaction mixture was filtered and the filtrate was concentrated. To the residue was added ethyl acetate and wash successively with 15% aqueous sodium hydroxide solution and water. The solvent was evaporated to give (2S)-2-(4-fluorophenyl)-4-(benzyl)morpholine (1.02 g, 92% yield) as a colorless oil.

1. temperaturethe reaction mixture was refluxed over 1.5 hrs
2. customthe reaction was quenched by addition of water (0.6 mL), 15% aqueous sodium hydroxide solution (0.6 mL) and water (1.8 mL) at 0° C
3. filtrationThe reaction mixture was filtered
4. concentrationthe filtrate was concentrated
5. additionTo the residue was added ethyl acetate
6. washwash successively with 15% aqueous sodium hydroxide solution and water
7. customThe solvent was evaporated

ORD record

ord-cfc8e4972cbe4906bd1deb971334ba69

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07994315B2