3,5-Dimethylpyrazole → 1-(3-Methoxyphenyl)-3,5-dimethyl-1H-pyrazole

HRID 1509644Notes

Reaction equation

I[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[CH:3]=1.[CH3:10][C:11]1[CH:15]=[C:14]([CH3:16])[NH:13][N:12]=1.C([O-])([O-])=O.[K+].[K+].[C@@H]1(N)CCCC[C@H]1N>O1CCOCC1.[Cu]I>[CH3:9][O:8][C:4]1[CH:3]=[C:2]([N:12]2[C:11]([CH3:10])=[CH:15][C:14]([CH3:16])=[N:13]2)[CH:7]=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 1-iodo-3-methoxybenzene (7.15 mL, 60 mmol, 1.0 eq), 3,5-dimethyl-1H-pyrazole (6.92 g, 72 mmol, 1.2 eq), CuI (0.46 g, 2.4 mmol, 0.04 eq), K2CO3 (17.41 g, 126 mmol, 2.1 eq), trans-1,2-cyclohexanediamine (1.37 g, 12 mmol, 0.2 eq) in dioxane (45 mL) was stirred at a temperature of 110° C. for 3.5 days under a nitrogen atmosphere and then cooled to ambient temperature. The solid was filtered off and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and the residue was purified through column chromatography on silica gel using hexane and ethyl acetate (10:1-3:1) as an eluent to obtain the desired product, 1-(3-methoxyphenyl)-3,5-dimethyl-1H-pyrazole 1, as a brown liquid (7.12 g in 59% yield). 1H NMR (DMSO-d6, 400 MHz): δ 2.18 (s, 3H), 2.30 (s, 3H), 3.80 (s, 3H), 6.06 (s, 1H), 6.95 (dd, J=8.0, 2.4 Hz, 1H), 7.02-7.06 (m, 2H), 7.39 (t, J=8.0 Hz, 1H).

Workup

temperaturecooled to ambient temperature
filtrationThe solid was filtered off
washwashed with ethyl acetate
concentrationThe filtrate was concentrated under reduced pressure
customthe residue was purified through column chromatography on silica gel

Sources & evidence

ORD record: ord-92c650b15e8945a19bc63890d306cb3e
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09224963B2

Reaction notes

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