Diethyl Ether → 4,4'-Difluorobenzophenone

Temperature

0 °C

To a solution of nitrile 1 (900 mg, 5.02 mmol) in ether (45 mL) at 0° C. was added via syringe ρ-fluorophenylmagnesium bromide (5.0 mL, 2.0 M solution in ether 10 mmol). The resulting turbid mixture was stirred at 0° C. for 5 min then warmed to r.t. and stirred for 6 h. At that time, the reaction was quenched with H2O (3 mL) and then diluted with ether (25 mL) and H2O (25 mL). The organic phase was separated, and the aqueous phase was extracted with ether (80 mL×2). The organic portions were combined, washed with saturated aqueous NaCl, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (30 g short path, 1%→10% EtOAc/hexane) to give the desired product (700 mg, 2.53 mmol, 50%) as a pale yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.97 (m, 2 H), 7.11 (m, 2 H), 5.79 (d, J=2.0 Hz, 1 H), 3.41 (s, 3 H), 2.97-2.81 (m, 3 H), 2.00 (m, 2 H), 1.82 (m, 1 H), 1.74 (m, 2 H), 1.65 (m, 1 H), 1.53 (m, 3 H), 1.21 (m, 1 H); 13C NMR (100 MHz, CDCl3) δ 199.0, 165.3 (d, J=253 Hz), 140.4, 133.7 (d, J=3.0 Hz), 130.4 (d, J=9.1 Hz), 118.8, 115.3 (d, J=22.0 Hz), 59.0, 36.6, 32.5, 31.6, 28.2, 26.4, 25.7, 21.6.

1. temperaturethen warmed to r.t.
2. stirringstirred for 6 h
3. customAt that time, the reaction was quenched with H2O (3 mL)
4. additiondiluted with ether (25 mL) and H2O (25 mL)
5. customThe organic phase was separated
6. extractionthe aqueous phase was extracted with ether (80 mL×2)
7. washwashed with saturated aqueous NaCl
8. dry with materialdried over anhydrous MgSO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe crude product was purified by column chromatography (30 g short path, 1%→10% EtOAc/hexane)

ORD record

ord-8b2f00f3e72a4f4bbff1cddc765d3da4

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06136847