Diethyl Ether → (3-Fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(4-fluorophenyl)methanone

To an oven-dried round-bottomed flask cooled at −78° C., was added 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (7.20 g, 24.82 mmol) in anhydrous ether (300 mL) under Argon, and the mixture was stirred at −78° C. for 10 min. n-BuLi (2.5 M in hexanes, 11.5 mL, 28.75 mmol, 1.16 eq) was added dropwise at −78° C. The reaction mixture was stirred at −78° C. for 45 min. An Et2O solution (20 mL) of 4-fluorobenzonitrile (3.06 g, 25.29 mmol, 1.02 eq) was added dropwise. The resulting reddish solution was stirred at −78° C. for 2 h. The reaction mixture was quenched by adding 1N HCl (200 mL), and the dry ice-acetone bath was removed. The resulting slurry was stirred at room temperature for 1 h followed by the addition of Et2O (100 mL). The organic layer was separated, and then washed with sat'd NaHCO3, H2O, brine, dried over MgSO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography (EtOAc/hexanes=0 to 30%) to give (3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(4-fluorophenyl)methanone as slightly tan oil (7.20 g, yield: 86.9%). 1H NMR (400 MHz, CDCl3) δ ppm 7.85-7.80 (m, 2H), 7.40-7.37 (m, 2H), 7.20-7.14 (m, 3H), 5.92 (tt, J=52, 2.8 Hz, 1H); LC-MS (ESI) 335.31 (M+H), retention time=3.81 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min run).

1. additionwas added dropwise at −78° C
2. stirringThe resulting reddish solution was stirred at −78° C. for 2 h
3. customThe reaction mixture was quenched
4. additionby adding 1N HCl (200 mL)
5. customthe dry ice-acetone bath was removed
6. stirringThe resulting slurry was stirred at room temperature for 1 h
7. additionfollowed by the addition of Et2O (100 mL)
8. customThe organic layer was separated
9. washwashed with sat'd NaHCO3, H2O, brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated to dryness
13. customThe residue was purified by flash chromatography (EtOAc/hexanes=0 to 30%)

ORD-Eintrag

ord-16d5ba43c5c74a38a9748e5479af34cf

Quelldatensatz

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08642576B2