Acetonitrile → HCID 46865763, compound

HRID 2390323Notes

Reaction equation

HRID 2390323 reaction equation
C([O:5][C:6](=[O:17])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1Br)(C)(C)C.[F:18][C:19]1(C#C)C=C[CH:22]=[CH:21][CH2:20]1.C(N([CH2:32][CH3:33])CC)C.[CH3:34][C:35]#N>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>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][C:6]([OH:5])=[O:17])=[C:10]([C:34]#[C:35][C:33]2[CH:32]=[CH:22][CH:21]=[CH:20][C:19]=2[F:18])[CH:11]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 49766393tert-Butyl (2-bromo-4-chlorophenoxy)acetate2×HCID 86659357HCID 86659357, compound

Product 1

HCID 46865763HCID 46865763, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
50 °C

Procedure

A solution of tert-butyl(2-bromo-4-chlorophenoxy)acetate (Intermediate 1; 350 mg; 1.09 mmol) and 1-fluorophenylacetylene (Aldrich, 135 μL; 1.20 mmol) in degassed, anhydrous CH3CN (2.80 mL) was treated with dichlorobis(triphenylphosphine)palladium(II) (38 mg; 0.05 mmol), copper(I) iodide (10 mg; 0.05 mmol) and triethylamine (0.45 mL; 3.26 mmol). The reaction mixture was heated at 50° C. under stirring for 16 hours. The solvent was evaporated and the residue purified by column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc. The purified ester intermediate was dissolved in DCM (6 mL) and an HCl solution (4 N in dioxane, 2.7 mL) was added. After stirring for 16 hours, the solvents were removed under vacuum and the crude product purified by preparative HPLC. The title compound was obtained as a light brown solid.

Workup

  1. customThe solvent was evaporated
  2. customthe residue purified by column chromatography (silica)
  3. washeluting with cyclohexane containing
  4. temperatureincreasing amounts of EtOAc
  5. dissolutionThe purified ester intermediate was dissolved in DCM (6 mL)
  6. additionan HCl solution (4 N in dioxane, 2.7 mL) was added
  7. stirringAfter stirring for 16 hours
  8. customthe solvents were removed under vacuum
  9. customthe crude product purified by preparative HPLC

Sources & evidence

ORD record
ord-5f6fd6f0468649bcab3206a505991d0c
Source dataset
uspto-grants-2012_09
Patent number
US08273769B2

Reaction notes

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