反応 #8584

反応方程式

6-chloro-2-picoline

ethyl 4-fluorobenzoate

lithium bis(trimethylsilyl)amide

→

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

収率 66.0%

溶媒

tetrahydrofuran

反応条件

後処理

1. 1
   その他over 1 hour
2. 2
   workup.ADDITIONUpon complete addition
3. 3
   その他the cold bath was removed
4. 4
   温度The mixture was cooled to room temperature
5. 5
   その他quenched by the addition of water
6. 6
   workup.ADDITIONEther was added
7. 7
   洗浄the organic layer was washed with brine
8. 8
   抽出The aqueous layer was extracted with ether
9. 9
   乾燥the combined organics were dried over magnesium sulfate
10. 10
    ろ過Filtration and concentration
11. 11
    その他gave a solid residue which
12. 12
    その他was purified by recrystallization from ethyl acetate-hexanes

実験手順

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).

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