Diethyl Ether → HCID 67970696, compound

HRID 889530Notes

Reaction equation

HRID 889530 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), methanol (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 aqueous NaCl, and separate the organic layer. Dry the organic layer over sodium sulfate, filter, and concentrate under reduced pressure. Subject the resulting crude material to chromatography on silica gel eluting with a 10-15% THF/hexanes gradient to give the title compound (6.19 g, 77%). GC/MS (m/z) 211 (M).

Workup

  1. customPurge
  2. washWash the mixture with water and saturated aqueous NaCl
  3. customseparate the organic layer
  4. dry with materialDry the organic layer over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-3b0c2e1bd6874a07b3738ffadebf457b
Source dataset
uspto-grants-2012_08
Patent number
US08252831B2

Reaction notes

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