Dimethylformamide → 3-formyl-1H-indole-6-carbonitrile

HRID 1512730Notes

Reaction equation

CN(C=O)C.[C:6](Cl)(=[O:10])[C:7](Cl)=O.[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:21]#[N:22])[CH:19]=2)C=[CH:13]1>ClCCl>[CH:6]([C:7]1[C:15]2[C:20](=[CH:19][C:18]([C:21]#[N:22])=[CH:17][CH:16]=2)[NH:12][CH:13]=1)=[O:10]

Participants

Conditions

Temperature: 0 °C

Procedure

DMF (0.389 mL) was added dropwise to a solution of oxalyl chloride (0.440 mL) in dry dichloromethane (5 mL) at 0° C. The resulting solution was stirred at 0° C. for 10 min. A solution of 1H-indole-6-carbonitrile (D12) (0.650 g) in dry dichloromethane (5 mL) was added to the reaction mixture. The reaction mixture was warmed to RT and stirred at that temperature for 45 min. The solvent was evaporated. THF (50 mL) was added, followed by addition of aqueous NaOH (2 M, 50 mL) and water (200 mL). The biphasic mixture was allowed to stand for 10 min. EtOAc (300 mL) and water (100 mL) was added. The organic fraction was separated and was dried over anhydrous magnesium sulfate. The dried solution was concentrated to afford 3-formyl-1H-indole-6-carbonitrile (D13) as a orange solid (604 mg). δH (DMSO-d6, 400 MHz): 7.59 (1H, dd), 8.05 (1H, d), 8.24 (1H, m), 8.56 (1H, s), 10.00 (1H, s), 12.62 (1H, br s). MS (ES): C10H6N2O requires 170; found 169.0 (M−H+).

Workup

temperatureThe reaction mixture was warmed to RT
stirringstirred at that temperature for 45 min
customThe solvent was evaporated
additionTHF (50 mL) was added
additionfollowed by addition of aqueous NaOH (2 M, 50 mL) and water (200 mL)
waitto stand for 10 min
additionEtOAc (300 mL) and water (100 mL) was added
customThe organic fraction was separated
dry with materialwas dried over anhydrous magnesium sulfate
concentrationThe dried solution was concentrated

Sources & evidence

ORD record: ord-3e529dbdc40b4c3894679eb12974b024
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217028B2

Reaction notes

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