Tetrahydrofuran → HCID 58495644, compound

HRID 1190994Notes

Reaction equation

HRID 1190994 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1.[CH:10]1([C:16]#[CH:17])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.C(N(CC)CC)C.C1COCC1>C([O-])(O)=O.[Na+].CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH:10]1([C:16]#[C:17][C:2]2[CH:3]=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 70263EthynylcyclohexaneHCID 8171545-Bromopyridine-2-carbonitrile

Product 1

HCID 58495644HCID 58495644, compoundYield 74.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Under a nitrogen atmosphere, add 5-bromo-2-cyano-pyridine (1.5 g, 8.2 mmol), cyclohexylacetylene (0.887 g, 8.2 mmol), dichlorobis(triphenylphosphine)palladium (575 mg, 0.82 mmol), copper(I) iodide (234 mg, 1.23 mmol) and triethylamine (11.4 mL, 82 mmol) to THF (50 mL). Heat the mixture to reflux and stir for 4 h. Cool the mixture to room temperature and dilute with saturated aqueous NaHCO3 (50 mL) and EtOAc (50 mL). Separate the layers and extract the aqueous layer with EtOAc (4×30 mL). Wash the combined organic extracts with brine (20 mL), dry over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (120 g, pre-packed cartridge) eluting with hexane/EtOAc (1:0 to 9:1 gradient over 1.25 h, 80 mL/min) to obtain the desired intermediate as a colorless oil (1.28 g, 74%). MS (APCI+) m/z: 211 (M H)+.

Workup

  1. temperatureHeat the mixture
  2. temperatureto reflux
  3. customSeparate the layers
  4. extractionextract the aqueous layer with EtOAc (4×30 mL)
  5. washWash the combined organic extracts with brine (20 mL)
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customPurify the crude mixture by chromatography on silica gel (120 g, pre-packed cartridge)
  10. washeluting with hexane/EtOAc (1:0 to 9:1 gradient over 1.25 h, 80 mL/min)

Sources & evidence

ORD record
ord-f5572eb542744722b35f0d2c7ef8d29c
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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