2,2-Difluoro-2-phenylacetamide → 2,2-Difluoro-2-phenylethylamine

Temperature

0 °C

2,2-Difluoro-2-phenylacetamide (2-9) (7.8 g, 45.03 mmol) was dissolved in THF (200 mL) and cooled to 0° C. with an ice bath. To this stirred solution was added 1M borane-tetrahydrofuran complex (315.2 mL, 315.2 mmol) dropwise over 15 minutes using a dropping funnel. The reaction mixture was aged until the ice bath expired. Upon expiration of the ice bath, the reaction mixture was heated to 70° C. overnight. The reaction mixture was allowed to cool to ambient temperature, then was quenched by the careful dropwise addition of water (100 mL). The mixture was concentrated in vacuo. The residue was diluted with dichloromethane (100 mL) and washed with 10% sodium carbonate. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude residue was purified by flash chromatography (ethyl acetate/hexane) (1:1 to 1:0 gradient) to afford the title compound (6.2 g, 86%) as a yellow oil. 1H-NMR (CDCl3): δ 3.15 (t, J=14.0 Hz, 2H), 7.41-7.45 (m, 5H).

1. additionTo this stirred solution was added 1M borane-tetrahydrofuran complex (315.2 mL, 315.2 mmol) dropwise over 15 minutes
2. temperatureto cool to ambient temperature
3. customwas quenched by the careful dropwise addition of water (100 mL)
4. concentrationThe mixture was concentrated in vacuo
5. additionThe residue was diluted with dichloromethane (100 mL)
6. washwashed with 10% sodium carbonate
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. concentrationconcentrated in vacuo
9. customThe crude residue was purified by flash chromatography (ethyl acetate/hexane) (1:1 to 1:0 gradient)

ORD record

ord-98f671baf82848a5b603f21932b7fe6b

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06777431B2