Aluminium lithium hydride → HCID 117871661, compound

Temperature

0 °C

(R)-6-(4-Fluoro-3-(trifluoromethyl)phenyl)morpholin-3-one (486 mg, 1.85 mmol) was dissolved in 2 mL of THF and 10 mL of ether. To this solution under ice bath was added powder LiAlH4 (72 mg, 1.85 mmol). The mixture was stirred at 0° C. for 1 h and then at room temperature overnight. LC/MS indicated only the starting material. To this mixture was added LiAlH4 (1M) in THF (2 mL, 2 mmol) under ice bath. The mixture was stirred at room temperature for 15 h. LC/MS indicated complete consumption of the starting material and the formation of the desired MW (250, M+1). Under ice bath, 2.5 mL of water was added and the mixture was stirred for 30 min. The top solution was decanted and concentrated. The slurry residue was treated with methylene chloride and water. The organic layer was combined with the dichloromethane solution from the decanted top solution, washed and dried. Solvents were evaporated to give (R)-2-(4-fluoro-3-(trifluoromethyl)phenyl)morpholine as a pale green oil (460 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.74 (dd, J=12.13, 10.36 Hz, 1H) 2.86-2.96 (m, 1H) 2.96-3.03 (m, 1H) 3.08 (dd, J=12.38, 2.53 Hz, 1H) 3.80 (td, J=11.37, 3.03 Hz, 1H) 4.06 (dd, J=11.37, 3.03 Hz, 1H) 4.52 (dd, J=10.36, 2.53 Hz, 1H) 7.14-7.23 (m, 1H) 7.50-7.58 (m, 1H) 7.64 (dd, J=6.69, 2.15 Hz, 1H).

1. customat room temperature
2. customovernight
3. stirringThe mixture was stirred at room temperature for 15 h
4. customconsumption of the starting material
5. additionUnder ice bath, 2.5 mL of water was added
6. stirringthe mixture was stirred for 30 min
7. customThe top solution was decanted
8. concentrationconcentrated
9. additionThe slurry residue was treated with methylene chloride and water
10. washwashed
11. customdried
12. customSolvents were evaporated

ORD record

ord-1135a28f373245e5aae21b33a15fd971

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09353096B2