Reaction #8600

Reaction equation

4-chloro-2-picoline

ethyl 4-fluorobenzoate

lithium bis(trimethylsilyl)amide

→

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

Yield 99.0%

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   Otherover 30 minutes
2. 2
   workup.ADDITIONUpon complete addition
3. 3
   Otherthe cold bath was removed
4. 4
   ConcentrationThe reaction mixture was concentrated under reduced pressure and methanol
5. 5
   workup.ADDITIONwas added to the reaction
6. 6
   Otherresulting in the formation of a white precipitate
7. 7
   FiltrationThe precipitate was collected by filtration
8. 8
   Otherdried

Procedure

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).

Source