N-methyl-2-pyrrolidone → 7-methyl-1H-indole-4-carbonitrile

HRID 475301Notes

Reaction equation

Br[C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[CH3:12][N:13]1C(=O)CCC1>[C-]#N.[C-]#N.[Zn+2].[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH3:11][C:8]1[C:7]2[NH:6][CH:5]=[CH:4][C:3]=2[C:2]([C:12]#[N:13])=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To a solution of 306 (300 mg, 1.43 mmol) in NMP (3 mL) under argon atmosphere were added Zn(CN)2 (167 mg, 1.43 mmol), zinc powder (18 mg, 0.28 mmol), Pd2(dba)3 (198 mg, 0.21 mmol), and dppf (237 mg, 0.42 mmol). After stirring at 140° C. for 18 h, the mixture was cooled and partitioned between ethyl EtOAc (200 mL) and water (50 mL). The organic layer was separated, washed with brine, dried (MgSO4), filtered, and evaporated in vacuo. The residue was purified by SiO2 chromatography eluting with 15% EtOAc/petroleum ether to afford 222 mg (85%) of 7-methyl-1H-indole-4-carbonitrile (308) as yellow solid.

Workup

temperaturethe mixture was cooled
custompartitioned between ethyl EtOAc (200 mL) and water (50 mL)
customThe organic layer was separated
washwashed with brine
dry with materialdried (MgSO4)
filtrationfiltered
customevaporated in vacuo
customThe residue was purified by SiO2 chromatography
washeluting with 15% EtOAc/petroleum ether

Sources & evidence

ORD record: ord-ef6b99eee2514118865d21981a616121
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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