Reacción #8600

Ecuación de reacción

4-chloro-2-picoline

ethyl 4-fluorobenzoate

lithium bis(trimethylsilyl)amide

→

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

Rendimiento 99.0%

Disolventes

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroover 30 minutes
2. 2
   workup.ADDITIONUpon complete addition
3. 3
   Otrothe cold bath was removed
4. 4
   ConcentraciónThe reaction mixture was concentrated under reduced pressure and methanol
5. 5
   workup.ADDITIONwas added to the reaction
6. 6
   Otroresulting in the formation of a white precipitate
7. 7
   FiltraciónThe precipitate was collected by filtration
8. 8
   Otrodried

Procedimiento

To a cold (0 ° C.) solution of 4-chloro-2-picoline (5.0 g,39 mmol) and ethyl 4-fluorobenzoate (6.6 g, 39 mmol) in tetrahydrofuran (100 mL) was added lithium bis(trimethylsilyl)amide (80 mL, 1.0 M in tetrahydrofuran, 80 mmol) dropwise via a pressure equalizing funnel over 30 minutes. Upon complete addition, the cold bath was removed and the resulting solution was stirred at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure and methanol was added to the reaction, resulting in the formation of a white precipitate. The precipitate was collected by filtration and dried to give 2-(4-chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone (9.6 g, 99%) as a white solid. 1H-NMR (DMSO-d6): δ 7.90 (m, 3H), 7.11 (t, 2H), 6.56 (s,1 H), 5.67 (s, 1 H), 4.14 (m, 2H); 19F-NMR (DMSO-d6): δ −115.67; MS m/z 250 (M+1).

Fuente