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

HRID 271297

Reaktionsgleichung

Reaktionsgleichung von HRID 271297
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

Komponenten

7

Edukt 5

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-6be534506db34de88a0cdc040fe279f4
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07452899B2

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