1H-1,2,4-Triazole → 3-Methyl-2-(1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile

HRID 587281Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH3:15])[C:5]([N:10]2[CH:14]=[N:13][CH:12]=[N:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8].Br[C:17]1C=C(C)C(F)=C([CH:24]=1)C#N.C([O-])([O-])=O.[K+].[K+].N1C=NC=N1>CN(C=O)C.O>[CH3:15][C:4]1[C:5]([N:10]2[CH:14]=[N:13][CH:12]=[N:11]2)=[C:6]([CH:9]=[C:2]([CH:17]=[CH2:24])[CH:3]=1)[C:7]#[N:8]

Participants

Conditions

Temperature: 140 °C

Procedure

5-Bromo-3-methyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (DI71): To a stirred solution of 5-bromo-2-fluoro-3-methylbenzonitrile (1.0 g, 47.716 mmol), in DMF (10.0 mL) was added K2CO3 (1.95 g, 14.14 mmol) followed by 1H-1,2,4-triazole (0.811 g, 9.433 mmol) at ambient temperature. The reaction mixture was heated to 140° C. for 18 h. The reaction mixture was cooled to ambient temperature, diluted with water and extracted with EtOAc (2×100 mL). The combined EtOAc layer was washed with brine and dried over Na2SO4 and concentrated under reduced pressure to afford the crude compound purified by flash column chromatography (SiO2, 100-200 mesh; eluting with 30% EtOAc/pet ether) to afford the title compound as a pink solid (0.6 g, 49%): 1H NMR (400 MHz, CDCl3) δ 8.39 (s, 1H), 8.23 (s, 1H), 7.91 (d, J=2.4 Hz, 2H), 2.21 (s, 3H), ESIMS m/z 262.57 ([M+H]+); IR (thin film) 2231, 554 cm−1.

Workup

temperatureThe reaction mixture was cooled to ambient temperature
extractionextracted with EtOAc (2×100 mL)
washThe combined EtOAc layer was washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
customto afford the crude compound
custompurified by flash column chromatography (SiO2, 100-200 mesh; eluting with 30% EtOAc/pet ether)

Sources & evidence

ORD record: ord-5ee47496f233451e8f3c4f40b3691210
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09226500B2

Reaction notes

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