Dichloromethane ethanol → 6-Chloro-2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-3-oxo-2,3-dihydro-1H-isoindole-4-carbonitrile

HRID 333218Notes

Reaction equation

HRID 333218 reaction equation
[F:1][C:2]1([F:26])[CH2:7][CH2:6][CH:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:22][C:21]4[C:16](=[C:17](I)[CH:18]=[C:19]([Cl:23])[CH:20]=4)[C:15]3=[O:25])[CH2:10][CH2:9]2)[CH2:4][CH2:3]1.[Cu][C:28]#[N:29].ClCCl.C(O)C>CN(C)C=O>[Cl:23][C:19]1[CH:18]=[C:17]([C:28]#[N:29])[C:16]2[C:15](=[O:25])[N:14]([CH:11]3[CH2:12][CH2:13][N:8]([CH:5]4[CH2:6][CH2:7][C:2]([F:26])([F:1])[CH2:3][CH2:4]4)[CH2:9][CH2:10]3)[CH2:22][C:21]=2[CH:20]=1

Participants

5

Reactant 3

HCID 21584144Dichloromethane ethanolHCID 671930032-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-5-chloro-7-iodo-2,3-dihydro-1H-isoindol-1-oneHCID 178418546HCID 178418546, compound

Product 1

HCID 696740676-Chloro-2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-3-oxo-2,3-dihydro-1H-isoindole-4-carbonitrileYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-5-chloro-7-iodo-2,3-dihydro-1H-isoindol-1-one (80 mg, 0.16 mmol) and copper(I) cyanide (22 mg, 0.24 mmol) were dissolved in N,N-dimethylformamide (1 mL) and the resulted solution was refluxed under nitrogen atmosphere for 3 hours. The solvent was removed under reduced pressure and the residue was diluted with dichloromethane and washed with 15% ammonium hydroxide. Organic phase was dried over sodium sulfate, filtered and evaporated. Column chromatography (dichloromethane/ethanol:95/5) afforded title compound (46 mg, 72% yield).

Workup

  1. temperaturethe resulted solution was refluxed under nitrogen atmosphere for 3 hours
  2. customThe solvent was removed under reduced pressure
  3. additionthe residue was diluted with dichloromethane
  4. washwashed with 15% ammonium hydroxide
  5. dry with materialOrganic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-a0487bacef4c4a249ceef1c129e6d711
Source dataset
uspto-grants-2014_11
Patent number
US08877944B2

Reaction notes

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