تفاعل #8584

معادلة التفاعل

6-chloro-2-picoline

ethyl 4-fluorobenzoate

lithium bis(trimethylsilyl)amide

→

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

المردود 66.0%

المذيبات

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرىover 1 hour
2. 2
   workup.ADDITIONUpon complete addition
3. 3
   أخرىthe cold bath was removed
4. 4
   درجة الحرارةThe mixture was cooled to room temperature
5. 5
   أخرىquenched by the addition of water
6. 6
   workup.ADDITIONEther was added
7. 7
   غسيلthe organic layer was washed with brine
8. 8
   استخلاصThe aqueous layer was extracted with ether
9. 9
   تجفيفthe combined organics were dried over magnesium sulfate
10. 10
    ترشيحFiltration and concentration
11. 11
    أخرىgave a solid residue which
12. 12
    أخرىwas purified by recrystallization from ethyl acetate-hexanes

الإجراء التجريبي

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).

المصدر