Water → 1-(5-fluoro-2-methoxy-4-nitrophenyl)-3-methyl-1H-1,2,4-triazole

HRID 1803104Notes

Reaction equation

[CH3:1][C:2]1[N:6]=[CH:5][NH:4][N:3]=1.F[C:8]1[CH:13]=[C:12]([F:14])[C:11]([N+:15]([O-:17])=[O:16])=[CH:10][C:9]=1[O:18][CH3:19].C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[F:14][C:12]1[C:11]([N+:15]([O-:17])=[O:16])=[CH:10][C:9]([O:18][CH3:19])=[C:8]([N:4]2[CH:5]=[N:6][C:2]([CH3:1])=[N:3]2)[CH:13]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Step B (1): A mixture of 3-methyl-1H-1,2,4-triazole (2.20 g, 26.4 mmol), 1,5-difluoro-2-methoxy-4-nitrobenzene (5.00 g, 26.4 mmol), and potassium carbonate (3.65 g, 26.4 mmol) in anhydrous DMSO (50 mL) was heated at 80° C. for 24 h. The reaction mixture was allowed to cool to rt and was poured into 500 mL of water/10 mL brine solution. The aqueous mixture was extracted with EtOAc (2×250 mL). The combined organic extracts were washed with water (500 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The crude reaction mixture was purified using silica gel column chromatography (50% EtOAc/hexane) to afford 1-(5-fluoro-2-methoxy-4-nitrophenyl)-3-methyl-1H-1,2,4-triazole (1.24 g, 18% yield). LC-MS (M+H)+=253.2. 1H NMR (500 MHz, chloroform-d) δ ppm 8.95 (s, 1 H) 8.00 (d, J=11.60 Hz, 1 H) 7.80 (d, J=6.10 Hz, 1 H) 4.09 (s, 3 H) 2.50 (s, 3 H).

Workup

temperatureto cool to rt
extractionThe aqueous mixture was extracted with EtOAc (2×250 mL)
washThe combined organic extracts were washed with water (500 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude reaction mixture
customwas purified

Sources & evidence

ORD record: ord-ce4cac5bf1174e9c8552c92390e66daf
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349880B2

Reaction notes

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