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

HRID 8488

反応式

HRID 8488 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
45 °C

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).

後処理

  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

出典と根拠

ORDレコード
ord-355d452942e54325bec58b0626c5dd9e
出典データセット
uspto-grants-2006_08
特許番号
US07087618B2

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