Tetrahydrofuran → (3-Fluoro-5-(trifluoromethyl)phenyl)(4-(trifluoromethyl)pyrimidin-2-yl)methanone

A mixture of 2-(methylsulfonyl)-4-(trifluoromethyl)pyrimidine (1.55 g, 6.63 mmol) and 2-(3-fluoro-5-(trifluoromethyl)phenyl)acetonitrile (1.53 g, 7.23 mmol) in anhydrous THF (45 mL) was stirred at room temperature under Argon. To the reaction mixture NaHMDS (8.8 mL, 1.0 M in THF, 8.8 mmol) was added during a 2-min period. The reaction mixture was stirred at room temperature for 1 h. 12 mL of the above reaction mixture was transferred to another round-bottomed flask. Saturated NH4Cl (10 mL) and THF (10 mL) were added, followed by the addition of Na2O2 (1.15 g, 14.7 mmol) at −30° C. The reaction mixture was stirred at room temperature for 5 h, followed by addition of MeOH. The solids were removed by filtration and the filtrate was concentrated. The residue was dissolved in EtOAc and the solution washed with H2O, saturated NaCl, dried over Na2SO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica gel, hexanes/EtOAc) to give pure (3-fluoro-5-(trifluoromethyl)phenyl)(4-(trifluoromethyl)pyrimidin-2-yl)methanone (0.45 g, 71.5% for two steps). NMR: 400 MHz 1H (CDCl3) 9.18 ppm, d, J=5.1 Hz, 1 H;, 8.08 ppm, s, 1 H;, 7.89 ppm, d, J=8.8 Hz, 1 H;, 7.81 ppm, d, J=5.1 Hz, 1 H;, 7.46 ppm, dt, J=7.8, 1.5 Hz, 1 H.

1. stirringThe reaction mixture was stirred at room temperature for 1 h
2. stirringThe reaction mixture was stirred at room temperature for 5 h
3. customThe solids were removed by filtration
4. concentrationthe filtrate was concentrated
5. dissolutionThe residue was dissolved in EtOAc
6. washthe solution washed with H2O, saturated NaCl
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated to dryness
10. customThe residue was purified by flash chromatography (silica gel, hexanes/EtOAc)

ORDレコード

ord-0730775c71c344f3a7501902edc733ad

出典データセット

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07888376B2