Hydrochloric Acid → 1-(2-Fluoropyridin-4-yl)-2-(3-trifluoromethylphenyl)ethane-1,2-dione-1-oxime

To a mixture of 2-(2-fluoropyridin-4-yl)-1-(3-trifluoromethyl-phenyl)ethanone (3) (10.80 g, 0.038 mol) in ethanol (200 mL), at −10° C., under argon, was added tert-butyl nitrite (5.0 mL, 0.042 mol) and hydrochloric acid (12.2 mL, 2.5M in ethanol, 0.031 mol) dropwise while maintaining the temperature below −5° C. Upon completion of additions, the reaction was allowed to warm to RT for 2 hrs. The reaction mixture was then concentrated in vacuo, diluted with water (100 mL), basified with saturated sodium bicarbonate (200 ml), and extracted with ethyl acetate (3×400 mL). The combined organic layers were washed with water (300 mL), dried with brine (300 mL) and anhydrous sodium sulfate, filtered and concentrated to an oil which weighed 11.4 g (95%). 1H NMR (300 MHz, CDCl3) d 8.31 (s, 1 H, Ar), 8.29 (d, J=5.3 Hz, 1 H, Pyr), 8.24 (d, J=7.8 Hz, 1 H, Ar), 7.92 (d, J=8.1 Hz, 1 H, Ar), 7.71 (t, J=7.8 Hz, 1 H, Ar), 7.40 (d, J=5.1 Hz, 1 H, Pyr), 7.23 (s, 1 H, Pyr).

1. temperaturewhile maintaining the temperature below −5° C
2. concentrationThe reaction mixture was then concentrated in vacuo
3. additiondiluted with water (100 mL)
4. extractionextracted with ethyl acetate (3×400 mL)
5. washThe combined organic layers were washed with water (300 mL)
6. dry with materialdried with brine (300 mL) and anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated to an oil which

ORD record

ord-ba0651fc93bc45169be5a5dc03f670c7

Source dataset

uspto-grants-2001_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06207687B1