Sodium bis(2-methoxyethoxy)aluminiumhydride → (3R)-4-Benzyl-3-methylmorpholine

Temperature

60 °C

To a solution of (5R)-5-methyl-4-(phenylmethyl)-3-morpholinone (11.7 g, 57 mmol) in toluene (140 mL) at 0° C. was added sodium bis(2-methoxyethoxy)aluminumhydride (Red-Al) (35 mL, 3 mL/g of morpholinone) slowly via addition funnel, and the reaction mixture was stirred overnight at 60° C. The reaction was cooled down to 0° C. and quenched by dropwise addition of 1N aqueous NaOH (15 mL). The resulting mixture was partitioned between Et2O (100 mL) and of 1N aqueous NaOH (100 mL). The organic layer was separated, and the aqueous layer was further extracted with Et2O (50 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated. The resulting residue was azeotroped with CH3OH (50 mL) to afford the title compound (10.69 g) as a colorless oil. LC-MS (ES) m/z=192 [M+H]+

1. additionslowly via addition funnel
2. temperatureThe reaction was cooled down to 0° C.
3. customquenched by dropwise addition of 1N aqueous NaOH (15 mL)
4. customThe resulting mixture was partitioned between Et2O (100 mL) and of 1N aqueous NaOH (100 mL)
5. customThe organic layer was separated
6. extractionthe aqueous layer was further extracted with Et2O (50 mL)
7. dry with materialThe combined organic layers were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe resulting residue was azeotroped with CH3OH (50 mL)

ORD record

ord-8b2b326a107943739a9b32061b3c2ab8

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697685B2