Reacción #8584

Ecuación de reacción

6-chloro-2-picoline

ethyl 4-fluorobenzoate

lithium bis(trimethylsilyl)amide

→

2-(6-chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone

Rendimiento 66.0%

Disolventes

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroover 1 hour
2. 2
   workup.ADDITIONUpon complete addition
3. 3
   Otrothe cold bath was removed
4. 4
   TemperaturaThe mixture was cooled to room temperature
5. 5
   Otroquenched by the addition of water
6. 6
   workup.ADDITIONEther was added
7. 7
   Lavadothe organic layer was washed with brine
8. 8
   ExtracciónThe aqueous layer was extracted with ether
9. 9
   Secadothe combined organics were dried over magnesium sulfate
10. 10
    FiltraciónFiltration and concentration
11. 11
    Otrogave a solid residue which
12. 12
    Otrowas purified by recrystallization from ethyl acetate-hexanes

Procedimiento

To a cold (0° C.) solution of 6-chloro-2-picoline (21.4 mL, 196.0 mmol) and ethyl 4-fluorobenzoate (57.5 mL, 391.2 mmol) in tetrahydrofuran (311 mL) was added lithium bis(trimethylsilyl)amide (391 mL, 1.0 M in tetrahydrofuran, 391.0 mmol) dropwise via a pressure equalizing funnel over 1 hour. Upon complete addition, the cold bath was removed and the resultant solution was heated to 45° C. for 15 hours. The mixture was cooled to room temperature and quenched by the addition of water. Ether was added and the organic layer was washed with brine. The aqueous layer was extracted with ether and the combined organics were dried over magnesium sulfate. Filtration and concentration gave a solid residue which was purified by recrystallization from ethyl acetate-hexanes to provide 2-(6-chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone (32.2 g, 66%) as a tinted off-white solid existing as a keto-enol tautomeric mixture. 1H NMR (CDCl3): for the keto tautomer δ 8.11 (m, 2 H), 7.66 (t, 1 H), 7.30–7.25 (m 2 H), 7.17 (t, 2 H), 4.48 (s 2 H), 19F NMR (CDCl3) δ −104.72 (keto), −111.64 (enol); MS m/z 250 (M+1).

Fuente