Aluminium lithium hydride → (3R)-4-Benzyl-3-methylmorpholine

A solution of (R)-4-benzyl-5-methylmorpholine-3-one (3.0 g, 14.22 mmol) in THF (10 mL) was added dropwise at 0° C. to a solution of lithium aluminum hydride (1.0 M solution in THF, 28.5 mL, 28.5 mmol) in THF (10 mL). The ice bath was removed and the reaction mixture was heated at reflux for 18 h. The reaction was cooled in an ice-bath and excess hydride reagent was quenched by careful, dropwise addition of H2O (5 mL), 15% sodium hydroxide (5 mL) and H2O (15 mL). The resulting mixture was stirred at room temperature for 1 h and the reaction mixture was filtered through a pad of Celite and the pad rinsed with EtOAc (100 mL). The filtrate was washed with saturated brine solution, dried (Na2SO4), filtered and concentrated under reduced pressure to provide (R)-4-benzyl-3-methylmorpholine (2.66 g, 95%) as a red oil. 1H NMR and MS consistent.

1. customThe ice bath was removed
2. temperaturethe reaction mixture was heated
3. temperatureat reflux for 18 h
4. temperatureThe reaction was cooled in an ice-bath
5. customexcess hydride reagent was quenched by careful,
6. additiondropwise addition of H2O (5 mL), 15% sodium hydroxide (5 mL) and H2O (15 mL)
7. filtrationthe reaction mixture was filtered through a pad of Celite
8. washthe pad rinsed with EtOAc (100 mL)
9. washThe filtrate was washed with saturated brine solution
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure

ORD record

ord-6fed043447574939af6f5a2cf375c9ca

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863271B2