N-methyl-2-pyrrolidone → 2,3-dihydro-3,3-dimethyl-1H-indole-6-carbonitrile

HRID 1475408Notes

Reaction equation

HRID 1475408 reaction equation
Cl[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:12])([CH3:11])[CH2:7][NH:8]2)=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[CH3:42][N:43]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N.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:6]1([CH3:12])[C:5]2[C:9](=[CH:10][C:2]([C:42]#[N:43])=[CH:3][CH:4]=2)[NH:8][CH2:7]1

Participants

6

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 204468746-chloro-3,3-dimethyl-2,3-dihydro-1H-indole

Product 1

HCID 107023412,3-dihydro-3,3-dimethyl-1H-indole-6-carbonitrileYield 15%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
185 °C

Procedure

6-Chloro-3,3-dimethyl-2,3-dihydro-1H-indole (1 g, 5.5 mmol), zinc cyanide (0.74 g, 6.3 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.2 g, 0.9 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.4 g, 1.1 mmol) were combined and dissolved in N-methyl-pyrrolidinone (27.6 mL). The suspension was degassed with nitrogen for 5 minutes. The reaction was heated under microwave irradiation for 2 h at 185° C. then cooled to room temperature and the reaction was diluted with water and extracted with diethyl ether/petrol (1:1) (3×). The combined organic extracts were washed with water and brine, dried over sodium sulfate and concentrated in vacuo. Chromatography (silica gel, gradient elution, 0-100%, EtOAc in petrol 40-60) gave the title compound (0.14 g, 15%) as pale yellow solid. MS: [M+H]+=173.

Workup

  1. customThe suspension was degassed with nitrogen for 5 minutes
  2. temperaturethen cooled to room temperature
  3. additionthe reaction was diluted with water
  4. extractionextracted with diethyl ether/petrol (1:1) (3×)
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. washChromatography (silica gel, gradient elution, 0-100%, EtOAc in petrol 40-60)

Sources & evidence

ORD record
ord-09a1434defe948b6841bd8bc00f29147
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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