Dimethylformamide dimethyl acetal → Ethyl 1-(3-cyano-4-fluorophenyl)-5-(2-furyl)pyrazole-4-carboxylate

HRID 1071488Notes

Reaction equation

HRID 1071488 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=O)[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].COC(OC)[N:17]([CH3:19])C.[Sn](Cl)(Cl)(Cl)Cl.[F:27][C:28]1[CH:33]=[CH:32][C:31]([NH:34]N)=[CH:30][C:29]=1[C:36]#[N:37]>C1C=CC=CC=1.C(O)(=O)C>[C:36]([C:29]1[CH:30]=[C:31]([N:34]2[C:6]([C:2]3[O:1][CH:5]=[CH:4][CH:3]=3)=[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:19]=[N:17]2)[CH:32]=[CH:33][C:28]=1[F:27])#[N:37]

Participants

6

Reactant 3

HCID 78373Dimethylformamide dimethyl acetalHCID 2759240Ethyl 3-(fur-2-yl)-3-oxopropanoateHCID 688056624-Fluoro-3-cyanophenylhydrazine tin chloride

Product 1

HCID 22288791Ethyl 1-(3-cyano-4-fluorophenyl)-5-(2-furyl)pyrazole-4-carboxylateYield 39%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 241BenzeneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl 3-(2-furyl)-3-ketopropionate (2.1 g, 11.5 mmol) in 20 mL of benzene was added dimethylformamide dimethylacetal (2.3 mL, 17.3 mmol). The resulting solution was stirred at 80° C. for 2 h. The reaction was cooled, filtered through a pad of silica gel and concentrated in vacuo. A portion of the residue (0.60 g, 2.54 mmol) was dissolved in 20 mL of glacial acetic acid and then there was added 4-fluoro-3-cyanophenylhydrazine tin chloride (1.05 g, 2.8 mmol). The reaction mixture was stirred at 100° C. for 4 h. The reaction was allowed to cool to room temperature and the acetic acid was removed in vacuo. The residue was diluted with ethyl acetate and the organics were washed with saturated aq NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography (elution with gradient of 6:1→3:1 hexanes/ethyl acetate) to afford 0.32 g (39%) of the title compound. LRMS (ES+): 326.2 (M+H)+.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered through a pad of silica gel
  3. concentrationconcentrated in vacuo
  4. stirringThe reaction mixture was stirred at 100° C. for 4 h
  5. temperatureto cool to room temperature
  6. customthe acetic acid was removed in vacuo
  7. additionThe residue was diluted with ethyl acetate
  8. washthe organics were washed with saturated aq NaHCO3 and brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography (elution with gradient of 6:1→3:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-bc367fc5355d4c658ac26f2ab43779af
Source dataset
uspto-grants-2005_06
Patent number
US06906070B2

Reaction notes

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