Bromine → 3-Bromo-2-methylindolizine-6-carbonitrile

HRID 216667

Reaction equation

[Br:1]Br.[CH3:3][C:4]1[CH:5]=[C:6]2[N:11]([CH:12]=1)[CH:10]=[C:9]([C:13]#[N:14])[CH:8]=[CH:7]2>CN(C)C=O.CCOC(C)=O.C([O-])(O)=O.[Na+]>[Br:1][C:12]1[N:11]2[C:6]([CH:7]=[CH:8][C:9]([C:13]#[N:14])=[CH:10]2)=[CH:5][C:4]=1[CH3:3]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of bromine (0.33 ml, 6.40 mmol. 1.0 equiv) in 10 ml of N,N-dimethylformamide is added under an atmosphere of argon at 0° C. to a solution of 2-methyl-indolizine-6-carbonitrile (1.0 g, 6.40 mmol) in 5 ml of N,N-dimethylformamide. The reaction mixture is heated in a microwave for 3 minutes at 80° C. After cooling, the reaction mixture is diluted with EtOAc and concentrated aqueous NaHCO3 solution. The aqueous phase is extracted three times with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the residue via flash chromatography (hexane/EtOAc 4:1, +0.2% NEt3) affords the title compound (1.0 g, 53%). 1H NMR (400 MHz, d6-DMSO): δ=8.97 (t, J=1.4 Hz, 1H), 7.56 (s, 1H), 7.28 (d, J=9.3 Hz, 1H), 6.87 (dd, J=9.3/1.5 Hz, 1H), 2.15 (d, J=1.0 Hz, 3H). MS (ES+): 236 (M+H)30.

Workup

temperatureAfter cooling
extractionThe aqueous phase is extracted three times with EtOAc
washThe combined organic layers are washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification of the residue via flash chromatography (hexane/EtOAc 4:1, +0.2% NEt3)

Sources & evidence

ORD record: ord-e5602914663c4050abe47d36fca8998f
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193236B2

Linked notes

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