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

HRID 475301
Notes
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Reaction equation

HRID 475301 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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 247292794-Bromo-7-methyl-1H-indole

Product 1

HCID 533993157-methyl-1H-indole-4-carbonitrileYield 85%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalyst
HCID 635956
Ferrocene-1,1'-bis-(diphenylphosphine)
Catalyst
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

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

  1. temperaturethe mixture was cooled
  2. custompartitioned between ethyl EtOAc (200 mL) and water (50 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by SiO2 chromatography
  9. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes