Tetrahydrofuran → 2-[4-(3-Ethyl-5-methyl-1H-pyrazol-1-yl)phenyl]ethanol

HRID 891132Notes

Reaction equation

HRID 891132 reaction equation
[C:1](Cl)(=O)[CH2:2][CH3:3].[C:6]([Mg]Br)#[C:7][CH3:8].O1CCCC1.C(=O)(O)[O-].[K+].Cl.[NH:22]([C:24]1[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][OH:32])=[CH:26][CH:25]=1)[NH2:23]>CCOCC.C(O)C>[CH2:7]([C:6]1[CH:1]=[C:2]([CH3:3])[N:22]([C:24]2[CH:25]=[CH:26][C:27]([CH2:30][CH2:31][OH:32])=[CH:28][CH:29]=2)[N:23]=1)[CH3:8]

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 62324Propionyl chlorideHCID 516893Potassium BicarbonateHCID 222447112-(4-Hydrazinophenyl)ethanol hydrochlorideHCID 178419101HCID 178419101, compound

Product 1

HCID 222446082-[4-(3-Ethyl-5-methyl-1H-pyrazol-1-yl)phenyl]ethanolYield 27%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of propionyl chloride (0.87 mL, 10 mmol) in ether (10 mL) was added a propynylmagnesium bromide 0.5 M solution in tetrahydrofuran (22 mL, 11 mmol) at 0° C. The resulting mixture was stirred at 0° C. for 1 h and then potassium bicarbonate was added. After filtered, ethanol (30 mL) and 2-(4-hydrazinophenyl)ethanol hydrochloride (490 mg, 2.5 mmol) were added. The mixture was heated under reflux overnight. After removal of the solvent, the resulting residue was partitioned between dichloromethane and water. Organic phase was washed with brine and dried (Na2SO4). After removal of the solvent, the crude product was purified by TLC with hexane/ethyl acetate (1:1) to afford 155 mg (27%) of the title compound as yellow oil: MS (EI) m/z 230 [M]+, 1H-NMR (CDCl3) δ 7.37-7.30 (4H, m), 6.02 (1H, s), 3.87 (2H, br.s), 2.91 (2H, br.s), 2.67 (2H, q, 6.5 Hz), 2.30 (3H, s), 1.27 (3H, t, 6.5 Hz).

Workup

  1. filtrationAfter filtered
  2. temperatureThe mixture was heated
  3. temperatureunder reflux overnight
  4. customAfter removal of the solvent
  5. customthe resulting residue was partitioned between dichloromethane and water
  6. washOrganic phase was washed with brine
  7. dry with materialdried (Na2SO4)
  8. customAfter removal of the solvent
  9. customthe crude product was purified by TLC with hexane/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-3889166d33bd4778a4faaba28338b2cf
Source dataset
uspto-grants-2006_02
Patent number
US07001917B2

Reaction notes

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