Benzoic acid, 4-fluoro-, ethyl ester → 2-(6-Chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone

HRID 8488

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HRID 8488 반응식
[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[CH:4][CH:3]=1.[F:9][C:10]1[CH:20]=[CH:19][C:13]([C:14](OCC)=[O:15])=[CH:12][CH:11]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>O1CCCC1>[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:14]([C:13]2[CH:19]=[CH:20][C:10]([F:9])=[CH:11][CH:12]=2)=[O:15])[CH:5]=[CH:4][CH:3]=1

참가 물질

5

반응물 3

HCID 67976Benzoic acid, 4-fluoro-, ethyl esterHCID 876016-Chloro-2-picolineHCID 2733832Lithium Hexamethyldisilazide

생성물 1

HCID 219486712-(6-Chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone수율 66%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
45 °C

실험 절차

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).

후처리

  1. customover 1 hour
  2. additionUpon complete addition
  3. customthe cold bath was removed
  4. temperatureThe mixture was cooled to room temperature
  5. customquenched by the addition of water
  6. additionEther was added
  7. washthe organic layer was washed with brine
  8. extractionThe aqueous layer was extracted with ether
  9. dry with materialthe combined organics were dried over magnesium sulfate
  10. filtrationFiltration and concentration
  11. customgave a solid residue which
  12. customwas purified by recrystallization from ethyl acetate-hexanes

출처 및 근거

ORD 기록
ord-355d452942e54325bec58b0626c5dd9e
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07087618B2

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