Hydrochloric Acid → 2-Fluoro-5-[2-(trimethylsilyl)ethynyl]benzenebutanenitrile

HRID 2240936Notes

Reaction equation

HRID 2240936 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:13])=[C:6]([CH2:8][CH2:9][CH2:10][C:11]#[N:12])[CH:7]=1.[CH3:14][Si:15]([C:18]#[CH:19])([CH3:17])[CH3:16].Cl>C(NCC)C.CN(C=O)C.C(OCC)(=O)C.[Cu]I.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>[F:13][C:5]1[CH:4]=[CH:3][C:2]([C:19]#[C:18][Si:15]([CH3:17])([CH3:16])[CH3:14])=[CH:7][C:6]=1[CH2:8][CH2:9][CH2:10][C:11]#[N:12]

Participants

9

Reactant 3

HCID 313Hydrochloric AcidHCID 66111TrimethylsilylacetyleneHCID 53434575HCID 53434575, compound

Product 1

HCID 593053672-Fluoro-5-[2-(trimethylsilyl)ethynyl]benzenebutanenitrileYield 71%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8021DiethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred solution of 4-(5-Bromo-2-fluoro-phenyl)-butyronitrile (0.37 g, 1.52 mmol) in diethyl amine (6 mL) and DMF (2 mL) was added triphenylphosine (0.08 g, 0.31 mmol), trimethylsilylacetylene (0.23 ml, 1.7 mmol), CuI (0.015 g, 0.076 mmol), and dichlorbis(triphenylphospine)palladium (0.054 g, 0.076 mmol). The reaction was heated at 85° C. for 12 h and then cooled to room temperature. The reaction was diluted with ethyl acetate (20 mL) and then poured into 0.1 N HCl (20 mL) and extracted with ethyl acetate (3×50 ml). The extracts were washed with water (10 mL) and brine (10 mL), dried (MgSO4) and concentrated in vacuo. Purification by flash chromatography (5% to 10% ethyl acetate/petroleum ether) gave the title compound as a clear oil (0.28 g, 70%), identified by NMR and mass spectral analyses; MS (ES+): 260 (M+H).

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with ethyl acetate (3×50 ml)
  3. washThe extracts were washed with water (10 mL) and brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography (5% to 10% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-18229ee87e7841919d5bf83793a2463e
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

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