Methanol → 4-Ethynyl-1-(4-methoxybenzyl)-1H-pyrazole

HRID 1042560Notes

Reaction equation

HRID 1042560 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[CH:6]=1.C[Si]([C:20]#[CH:21])(C)C.CO.[OH-].[K+]>C(Cl)Cl.C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:20]([C:2]1[CH:3]=[N:4][N:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[CH:6]=1)#[CH:21]

Participants

9

Reactant 4

HCID 887MethanolHCID 14797Potassium HydroxideHCID 66111TrimethylsilylacetyleneHCID 574219364-iodo-1-[(4-methoxyphenyl)methyl]-1H-pyrazole

Product 1

HCID 574219374-Ethynyl-1-(4-methoxybenzyl)-1H-pyrazoleYield 81.5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

A vigorously stirred solution of 4-iodo-1-(4-methoxy-benzyl)-1H-pyrazole (1.0 g, 3.18 mmol) and Pd(Ph3P)2Cl2 (60 mg, 3 mol %) in a mixture of DCM (10 mL) and triethylamine (3 mL) was evacuated and backfilled with nitrogen three times and then treated sequentially with trimethylsilylacetylene (0.53 mL, 3.83 mmol) and copper (I) iodide (70 mg, 12 mol %). The reaction rapidly became dark and after stirring for 3 h the solvents were removed in vacuo and the residue treated with methanol (10 mL) and potassium hydroxide (300 mg, 5.35 mmol). After stirring for 30 minutes the mixture was concentrated onto silica gel and purified by flash column chromatography (eluent-hexane:diethyl ether 2:1) to afford the title compound as a white solid (550 mg, 81% yield over two steps). 1H-NMR (CDCl3) δ 7.61 (s, 1H), 7.46 (s, 1H), 7.17 (d, J=8.6 Hz, 2H), 6.86 (d, J=8.6 Hz, 2H), 5.18 (s, 2H), 3.78 (s, 3H), 2.96 (s, 1H).

Workup

  1. customwas evacuated
  2. customThe reaction rapidly became dark
  3. customwere removed in vacuo
  4. stirringAfter stirring for 30 minutes the mixture
  5. concentrationwas concentrated onto silica gel
  6. custompurified by flash column chromatography (eluent-hexane:diethyl ether 2:1)

Sources & evidence

ORD record
ord-fa12056f6b03409a992d704fe55df00c
Source dataset
uspto-grants-2013_10
Patent number
US08557982B2

Reaction notes

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