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

HRID 475114Notes

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 4-bromo-2-methyl-1H-indole (572 mg, 2.72 mmol), Zn(CN)2 (351 mg, 3.0 mmol), Zn (35 mg, 0.54 mmol), dppf (606 mg, 1.09 mmol), and Pd2(dba)3 (498 mg, 0.54 mmol) in NMP (10 mL) under argon atmosphere was heated at 120° C. for 18 h. After cooling to RT, the reaction mixture was partitioned between EtOAc (300 mL) and water (50 mL). The organic layer was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with petroleum ether/EtOAc (3:1) to afford 2-methyl-1H-indole-4-carbonitrile as a yellow oil (408 mg, 96%). MS (ESI): m/z=157.2 [M+1]+.

Workup

temperatureAfter cooling to RT
customthe reaction mixture was partitioned between EtOAc (300 mL) and water (50 mL)
washThe organic layer was washed with brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by SiO2 chromatography
washeluting with petroleum ether/EtOAc (3:1)

Sources & evidence

ORD record: ord-6e3d0cb2a7324c2ba74ccd588c588a64
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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