Water → 1-(2-methoxy-4-nitrophenyl)-4-methyl-1H-imidazole

HRID 475716

Reaction equation

[CH3:1][C:2]1[N:3]=[CH:4][NH:5][CH:6]=1.Cl[C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][C:9]=1[O:17][CH3:18].[OH-].[K+].O>CS(C)=O>[CH3:18][O:17][C:9]1[CH:10]=[C:11]([N+:14]([O-:16])=[O:15])[CH:12]=[CH:13][C:8]=1[N:5]1[CH:6]=[C:2]([CH3:1])[N:3]=[CH:4]1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 4-methyl-1H-imidazole (18.0 g, 53.5 mmol), 1-chloro-2-methoxy-4-nitrobenzene (10.0 g, 53.5 mmol), and potassium hydroxide (4.5 g, 80.3 mmol) in DMSO (50 mL) was heated at 110° C. for 24 h. The reaction mixture was allowed to cool to rt and was poured into 1000 mL of water. The aqueous mixture was extracted with dichloromethane (3×250 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude reaction mixture was purified using silica gel chromatography (330 g silica cartridge, 0-2% MeOH/chloroform, linear gradient over 72 min, flow 25 mL/min) to afford 1-(2-methoxy-4-nitrophenyl)-4-methyl-1H-imidazole (2.56 g, 20% yield) as a yellow/orange solid. LC-MS (M+H)+=234.1. 1H NMR (500 MHz, CDCl3) δ ppm 7.97-8.00 (m, 1H) 7.93-7.97 (m, 2H) 7.45 (d, J=8.85 Hz, 1H) 7.02 (s, 1H) 4.02 (s, 3H) 2.35 (s, 3H).

Workup

temperatureto cool to rt
extractionThe aqueous mixture was extracted with dichloromethane (3×250 mL)
washThe combined organic extracts were washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude reaction mixture
customwas purified
customsilica gel chromatography (330 g silica cartridge, 0-2% MeOH/chloroform, linear gradient over 72 min, flow 25 mL/min)

Sources & evidence

ORD record: ord-ca0ee2577273421dbefc3b77a3674f24
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637525B2

Linked notes

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