Water → HCID 76846734, compound

HRID 475297Notes

Reaction equation

HRID 475297 reaction equation
Br[C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.O.[CH3:13][N:14]1C(=O)CCC1>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].[C-]#N.[C-]#N.[Zn+2].[Zn]>[CH3:11][C:10]1[CH:9]=[CH:8][C:7]2[NH:6][CH:5]=[CH:4][C:3]=2[C:2]=1[C:13]#[N:14]

Participants

8

Reactant 3

HCID 962WaterHCID 13387N-methyl-2-pyrrolidoneHCID 104886354-bromo-5-methyl-1H-indole

Product 1

HCID 76846734HCID 76846734, compoundYield 48.5%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
145 °C

Procedure

A mixture of 300 (150 mg, 0.714 mmol), Pd2(dba)3 (131 mg, 0.143 mmol), dppf (159 mg, 0.286 mmol), Zn(CN)2 (84 mg, 0.714 mmol), and zinc (4.6 mg, 0.0714 mmol) in NMP (10 mL) under nitrogen atmosphere was heated at 145° C. for 18 h. The reaction mixture was poured into water (50 mL) and extracted with EtOAc (20 mL×3). The combined extracts were dried (MgSO4), filtered, and concentrated to dryness. The crude was purified by SiO2 chromatography eluting with petroleum ether/EtOAc (3:1) to afford 54 mg (48.5%) 5-methyl-1H-indole-4-carbonitrile (302) as yellow solid: MS (ESI) m/z=157.1 (M+1).

Workup

  1. extractionextracted with EtOAc (20 mL×3)
  2. dry with materialThe combined extracts were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customThe crude was purified by SiO2 chromatography
  6. washeluting with petroleum ether/EtOAc (3:1)

Sources & evidence

ORD record
ord-4ba6f4090e054926b2486999ec10724f
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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