Hydroxyamine hydrochloride → (4-Fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone oxime

Temperature

100 °C

To a solution of (4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone, prepared as described in Procedure 3, 4, 59 and 68, (207 mg, 0.53 mmol) in pyridine (1.5 mL) was added hydroxylamine hydrochloride (192 mg, 2.8 mmol) and the reaction mixture was heated at 100° C. for 2 h. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in EtOAc (50 mL). The organic portion was washed with 1 N HCl (2×20 mL), water (20 mL) and sat. NaCl (20 mL), then dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by ISCO (40 g silica gel column, 0-30% EtOAc/hexane over 30 min) to yield (4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone oxime (216 mg, 77% yield) as a colorless oil. LCMS: RT=2.13 min [M+H] 408.2 (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).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in EtOAc (50 mL)
3. washThe organic portion was washed with 1 N HCl (2×20 mL), water (20 mL) and sat. NaCl (20 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by ISCO (40 g silica gel column, 0-30% EtOAc/hexane over 30 min)

ORD record

ord-2741a1e83618413786cbb925e3d9ac37

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642576B2