Dimethylformamide → HCID 21904630, compound

HRID 1191021Notes

Reaction equation

HRID 1191021 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[N:12][C:13](Cl)=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:17][N:18](C=O)C>O.CCOC(C)=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].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:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[N:12][C:13]([C:17]#[N:18])=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 2

HCID 6228DimethylformamideHCID 15449580Tert-butyl [(6-chloropyridin-3-yl)methyl]carbamate

Product 1

HCID 21904630HCID 21904630, compoundYield 90%

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Under a nitrogen atmosphere, add 3-(tert-butoxycarbonylamino-methyl)-6-chloropyridine (13.1 g, 54 mmol), zinc cyanide (9.5 g, 81 mmol), tris(dibenzylideneacetone)dipalladium(0) (494 mg, 0.54 mmol), and dppf (550 mg, 0.81 mmol) to DMF (130 mL). Heat the mixture at 70° C. overnight. Cool the mixture to room temperature and dilute with water and EtOAc. Separate the layers, and extract the aqueous layer with EtOAc. Wash the combined organic extracts with water and brine. Dry the organic solution over Na2SO4, filter, and concentrate in vacuo. Purify by chromatography on silica gel (500 g) eluting with hexane/EtOAc (1:0 to 7:3 gradient) to provide the desired intermediate as a white solid (11.3 g, 90%). MS (ES+) m/z: 234 (M+H)+.

Workup

  1. temperatureCool the mixture to room temperature
  2. customSeparate the layers
  3. extractionextract the aqueous layer with EtOAc
  4. washWash the combined organic extracts with water and brine
  5. dry with materialDry the organic solution over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify by chromatography on silica gel (500 g)
  9. washeluting with hexane/EtOAc (1:0 to 7:3 gradient)

Sources & evidence

ORD record
ord-77a29fa14eb84c5d922b3d33b491c23a
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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