Dimethylformamide → HCID 58001719, compound

HRID 420712Notes

Reaction equation

HRID 420712 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][OH:10])[CH:5]=[N:6][C:7]=1Cl.CC(OC)(C)C.C([O-])([O-])=O.[Na+].[Na+].[CH3:23][N:24](C=O)C>CCCCCC.CCOC(C)=O.[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:7]([C:23]#[N:24])=[N:6][CH:5]=[C:4]([CH2:9][OH:10])[CH:3]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 15413tert-Butyl methyl etherHCID 21882961(5,6-Dichloropyridin-3-yl)methanol

Product 1

HCID 58001719HCID 58001719, compoundYield 28%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

Zn(CN)2 (64.3 mg, 0.548 mmol) and Pd(PPh3)4 (84 mg, 0.073 mmol) were added to a solution of 5,6-dichloro-3-pyridinemethanol (130 mg, 0.730 mmol) in anhydrous DMF (1.5 ml) under N2 and the mixture was heated at 95° C. overnight. Low conversion was observed by HPLC. After heating under reflux for 2 h, the conversion did not increase, so additional Pd(PPh3)4 (84 mg, 0.073 mmol) was added. Two more h under reflux gave full conversion. TBME, and 10% Na2CO3 were added. Extraction, drying (MgSO4), filtration, and removal of the solvent afforded the crude product. Purification by flash chromatography using Flashmaster II, a 5 g spherical silica gel cartridge, and mixtures of hexane and EtOAc as an eluent afforded 3-chloro-5-(hydroxymethyl)-2-pyridinecarbonitrile (34.6 mg, 0.205 mmol, 28% yield) as a pale yellow solid.

Workup

  1. temperatureAfter heating
  2. temperatureunder reflux for 2 h
  3. temperaturethe conversion did not increase
  4. temperatureTwo more h under reflux
  5. customgave full conversion
  6. extractionExtraction
  7. customdrying
  8. filtration(MgSO4), filtration, and removal of the solvent
  9. customafforded the crude product
  10. customPurification by flash chromatography

Sources & evidence

ORD record
ord-dadbd732b2804f5f88c72c4a7c3a4b82
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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