Réaction #8584

Équation de réaction

6-chloro-2-picoline

ethyl 4-fluorobenzoate

lithium bis(trimethylsilyl)amide

→

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

Rendement 66.0%

Solvants

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   Autreover 1 hour
2. 2
   workup.ADDITIONUpon complete addition
3. 3
   Autrethe cold bath was removed
4. 4
   TempératureThe mixture was cooled to room temperature
5. 5
   Autrequenched by the addition of water
6. 6
   workup.ADDITIONEther was added
7. 7
   Lavagethe organic layer was washed with brine
8. 8
   ExtractionThe aqueous layer was extracted with ether
9. 9
   Séchagethe combined organics were dried over magnesium sulfate
10. 10
    FiltrationFiltration and concentration
11. 11
    Autregave a solid residue which
12. 12
    Autrewas purified by recrystallization from ethyl acetate-hexanes

Mode opératoire

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).

Source