Dimethylformamide → 7-(Benzyloxy)-1-(2-methoxyethyl)-2-methyl-1H-benzimidazole-5-carbonitrile

HRID 1258454Notes

Reaction equation

[CH2:1]([O:8][C:9]1[C:14]2[N:15]([CH2:19][CH2:20][O:21][CH3:22])[C:16]([CH3:18])=[N:17][C:13]=2[CH:12]=[C:11](Br)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:30][N:31](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:8][C:9]1[C:14]2[N:15]([CH2:19][CH2:20][O:21][CH3:22])[C:16]([CH3:18])=[N:17][C:13]=2[CH:12]=[C:11]([C:30]#[N:31])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 7-(benzyloxy)-5-bromo-1-(2-methoxyethyl)-2-methyl-1H-benzimidazole (1.00 g, 2.66 mmol, Step 3), zinc cyanide (376 mg, 3.20 mmol), and tetrakis(triphenylphosphine)palladium (154 mg, 0.13 mmol) in N,N-dimethylformamide (15 mL) was stirred at 90° C. for 3 hours under nitrogen gas. After cooling to room temperature, the mixture was poured onto saturated potassium carbonate aqueous solution (100 mL), and the aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over magnesium sulfate, and concentrated in vacuo. The residual solid was washed with ethyl acetate/diisopropyl ether (1:2) to afford the title compound as a white solid (648 mg, 76%).

Workup

temperatureAfter cooling to room temperature
extractionthe aqueous layer was extracted with ethyl acetate
dry with materialThe combined organic layer was dried over magnesium sulfate
concentrationconcentrated in vacuo
washThe residual solid was washed with ethyl acetate/diisopropyl ether (1:2)

Sources & evidence

ORD record: ord-a44b288d27274e36a38c5d042c750779
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08466166B2

Reaction notes

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