Diethyl Ether → HCID 67970696, compound

HRID 241436Notes

Reaction equation

HRID 241436 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH:10]([F:12])[F:11])[C:5]#[N:6].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C]=[O:50].C[CH2:52][O:53][CH2:54]C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C.CO>[C:5]([C:4]1[CH:7]=[CH:8][C:9]([CH:10]([F:12])[F:11])=[C:2]([CH:3]=1)[C:52]([O:53][CH3:54])=[O:50])#[N:6]

Participants

9

Reactant 5

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 67970619HCID 67970619, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 67970696HCID 67970696, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Purge a mixture of 3-bromo-4-(difluoromethyl)benzonitrile (8.87 g, 38.2 mmol, 1.0 equiv), triethylamine (16.0 mL, 114.7 mmol, 3.0 equiv), MeOH (70 mL), and DMF (120 mL) with nitrogen; then treat the mixture with palladium(II) acetate (867 mg, 3.82 mmol, 0.1 equiv) and 1,3-bis(diphenylphosphino)propane (1.61 g, 3.82 mmol, 0.1 equiv). Stir the mixture under 138 kPag of carbon monoxide at room temperature for two days and then 80° C. for one day. Cool the mixture to room temperature, and dilute with Et2O (300 mL). Wash the mixture with water and saturated sodium chloride, and separate the organic layer. Dry the organic layer over sodium sulfate; filter; collect the filtrate; and concentrate under reduced pressure. Subject the resulting crude material to silica gel chromatography eluting with a gradient of 10-15% THF/hexanes gradient to give the title compound (6.19 g, 77% yield). ES/MS (m/z) 211 (M).

Workup

  1. customPurge
  2. washWash the mixture with water and saturated sodium chloride
  3. customseparate the organic layer
  4. dry with materialDry the organic layer over sodium sulfate
  5. filtrationfilter
  6. customcollect the filtrate
  7. concentrationand concentrate under reduced pressure
  8. washeluting with a gradient of 10-15% THF/hexanes gradient

Sources & evidence

ORD record
ord-5f5bb4786d9242949fde6abeaade1c95
Source dataset
uspto-grants-2014_02
Patent number
US08648200B2

Reaction notes

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