Propargyl alcohol → 3-[4-(3-Hydroxy-prop-1-ynyl)-phenyl]-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one

HRID 1617517Notes

Reaction equation

HRID 1617517 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)=[O:11])=[CH:4][CH:3]=1.[CH2:26]([OH:29])[C:27]#[CH:28]>C(N(CC)CC)C.[Cu]I>[OH:29][CH2:26][C:27]#[C:28][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)=[O:11])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 7859Propargyl alcoholHCID 666681803-(4-Bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one

Product 1

HCID 666687223-[4-(3-Hydroxy-prop-1-ynyl)-phenyl]-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-oneYield 70%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8471TriethylamineSolvent

Procedure

To 3-(4-bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one ((example 74, step 5), 400 mg) in triethylamine (4.1 mL) tetrakis(triphenylphosphine)palladium (59 mg) and CuI (10 mg) were added. At 80° C. 2-propyn-1-ol (0.12 mL) was added slowly, and the solution was stirred at that temperature for 3 hours. The solution was concentrated in vacuo and redissolved in EtOAc and a saturated solution of NH4Cl. The phases were separated and the inorganic one extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (EtOAc/n-heptane 2:1) to yield the title compound (264 mg, 70%) as a yellow oil, MS (ESI+): m/z=370.1 ([M+H]+).

Workup

  1. customAt 80° C
  2. concentrationThe solution was concentrated in vacuo
  3. dissolutionredissolved in EtOAc
  4. customThe phases were separated
  5. extractionthe inorganic one extracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash chromatography on silica gel (EtOAc/n-heptane 2:1)

Sources & evidence

ORD record
ord-487bf82a488c47b5b6f43b5c8d3a4c21
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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