Ammonium Acetate → (3-Fluoro-5-(trifluoromethyl)phenyl)(4-fluorophenyl)methanamine

To a suspension of (3-fluoro-5-(trifluoromethyl)phenyl)(4-fluorophenyl)methanone oxime (904 mg, 3.0 mmol) in EtOH (3 mL) and conc. NH4OH (15 mL) was added ammonium acetate (120 mg, 1.6 mmol) followed by zinc powder (1.05 g, 16.2 mmol) and the reaction mixture was heated at reflux for 2 h. The reaction mixture was allowed to cool to rt then filtered. The filtered solid was washed with 10 N NaOH (15 mL) and EtOAc (15 mL). The combined filtrate was extracted with EtOAc (2×30 mL). The combined organic fractions were washed with sat. NaCl (2×10 mL) then dried over MgSO4, filtered and concentrated under reduced pressure to yield (3-fluoro-5-(trifluoromethyl)phenyl)(4-fluorophenyl)methanamine (804 mg, 93% yield) as a clear, colorless oil. LCMS: RT=0.96 min [M−NH2] 271.0 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% acetonitrile/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H (CDCl3) δ ppm 1.68 (bs, 2H), 5.25 (s, 1H), 7.03 (t, J=8.57 Hz, 2H), 7.19 (d, J=7.91 Hz, 1H), 7.29-7.35 (m, 3H), 7.48 (s, 1H).

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 2 h
3. filtrationthen filtered
4. washThe filtered solid was washed with 10 N NaOH (15 mL) and EtOAc (15 mL)
5. extractionThe combined filtrate was extracted with EtOAc (2×30 mL)
6. washThe combined organic fractions were washed with sat. NaCl (2×10 mL)
7. dry with materialthen dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure

ORD record

ord-6bde5b663b2c409ca155d344c030211b

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642576B2