Acetic Acid → 5-(4-fluorophenyl)-1-methyl-1H-pyrazol-3-carboxaldehyde dimethyl acetal

HRID 271297ノート

反応式

HRID 271297 の反応式
C([N-]C(C)C)(C)C.[Li+].[CH3:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)=O.[CH3:19][O:20][CH:21]([O:26][CH3:27])[C:22](OC)=O.C(O)(=O)C.[CH3:32][NH:33][NH2:34]>C1COCC1>[CH3:19][O:20][CH:21]([O:26][CH3:27])[C:22]1[CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[N:33]([CH3:32])[N:34]=1

参加物

7

反応物 5

HCID 176Acetic AcidHCID 6061MethylhydrazineHCID 98284'-FluoroacetophenoneHCID 66647Acetic acid, 2,2-dimethoxy-, methyl esterHCID 2724682Lithium diisopropylamide

生成物 1

HCID 586948315-(4-fluorophenyl)-1-methyl-1H-pyrazol-3-carboxaldehyde dimethyl acetal

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
25 °C

実験手順

To a solution of lithium diisopropylamide (1.8M in THF, 160 mL, 0.29 mol) at −78° C. was added 4-fluoroacetophenone (17.6 mL, 0.145 mol) in THF (150 mL), dropwise. The reaction was stirred at −78° C. for 1 h before the addition of methyl dimethoxyacetate (17.7 mL, 0.145 mol) in THF (150 mL). The reaction was warmed to 25° C. and stirred for 16 h. The solvent was removed in vacuo and the residue taken up in EtOH (250 mL), acetic acid (17 mL, 0.3 mol) added, followed by methyl hydrazine (8 mL) and the reaction heated to reflux for 2 h. The ethanol was removed in vacuo and the residue extracted with dichloromethane (×3), the organic layer washed with brine, dried over MgSO4 and concentrated. The residue was chromatographed on silica eluting with 50% ethyl acetate/hexanes to give the title compound (more polar isomer) along with its isomer (less polar). 9 g 1H NMR (360, CDCl3) δ 7.38 (m, 2H), 7.14 (m, 2H), 6.34 (s, 1H), 5.48 (s, 1H), 3.85 (s, 3H), 3.43 (s, 6H).

後処理

  1. customThe solvent was removed in vacuo
  2. temperaturethe reaction heated
  3. temperatureto reflux for 2 h
  4. customThe ethanol was removed in vacuo
  5. extractionthe residue extracted with dichloromethane (×3)
  6. washthe organic layer washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was chromatographed on silica eluting with 50% ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-6be534506db34de88a0cdc040fe279f4
出典データセット
uspto-grants-2008_11
特許番号
US07452899B2

反応ノート

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