N-methyl-2-pyrrolidone → HCID 58403540, compound

HRID 475267Notes

Reaction equation

HRID 475267 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH3:11])=[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:4]1[C:3]2[C:2]([C:12]#[N:13])=[CH:10][CH:9]=[CH:8][C:7]=2[NH:6][CH:5]=1

Participants

7

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 529877044-Bromo-3-methyl-1H-indole

Product 1

HCID 58403540HCID 58403540, compoundYield 59%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
140 °C

Procedure

To a solution of 230 (454 mg, 2.16 mmol) in NMP (4.5 mL) under argon atmosphere was added Zn(CN)2 (252 mg, 2.16 mmol), zinc powder (27 mg, 0.43 mmol), Pd2(dba)3 (0) (293 mg, 0.32 mmol), and dppf (358 mg, 0.65 mmol). The solution was heated at 140° C. for 18 h, the mixture was cooled and partitioned between EtOAc (100 mL) and H2O (30 mL). The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated to dryness in vacuo. The residue was purified by SiO2 chromatography eluting with 10% EtOAc/petroleum ether to afford 200 mg (59%) of 3-methyl-1H-indole-4-carbonitrile (232) as white solid: MS (ESI) m/z=157.1 [M+1]+.

Workup

  1. temperaturethe mixture was cooled
  2. custompartitioned between EtOAc (100 mL) and H2O (30 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated to dryness in vacuo
  8. customThe residue was purified by SiO2 chromatography
  9. washeluting with 10% EtOAc/petroleum ether

Sources & evidence

ORD record
ord-95a18e6ebff34a0c94968929095ef21b
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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