Ammonium Acetate → (4-Fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanamine

To a suspension of (4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone oxime (3.5 g, 8.6 mmol) in EtOH (30 mL) and conc. NH4OH (50 mL) was added ammonium acetate (754 mg, 19.8 mmol), followed by zinc powder (3.2 g, 49.1 mmol) and the reaction mixture was heated at reflux for 3 h. The reaction mixture was allowed to cool to rt then filtered through celite. The solid was washed with 1 N NaOH (10 mL) and MeOH (10 mL). The combined filtrate was extracted concentrated and the residue was partitioned between EtOAc and water. The organic layer was separated and washed with 1 N NaOH (15 mL), sat. NaCl (2×10 mL), dried over MgSO4, filtered and concentrated under reduced pressure to yield (4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanamine (2.8 g, 83% yield) as a light yellow oil. LCMS: RT=1.76 min [M-NH2] 377.1 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); 1H NMR (400 MHz, CDCl3) δ ppm 6.97-7.09 (4H, m), 6.81-6.89 (2H, m), 5.76-6.03 (1H, m), 5.14 (1H, s), 4.52 (1H, ddd, J=11.97, 6.15, 6.04 Hz), 1.73 (2H, bs), 1.29-1.36 (6H, m).

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 3 h
3. filtrationthen filtered through celite
4. washThe solid was washed with 1 N NaOH (10 mL) and MeOH (10 mL)
5. extractionThe combined filtrate was extracted
6. concentrationconcentrated
7. customthe residue was partitioned between EtOAc and water
8. customThe organic layer was separated
9. washwashed with 1 N NaOH (15 mL), sat. NaCl (2×10 mL)
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure

ORDレコード

ord-bcabadfe17b545d8a2e29418c080fe3c

出典データセット

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08304403B2