Triphenylphosphine → 4-(2,4-Dimethoxyphenyl)-but-3-yn-1-ol

HRID 1294545Notes

Reaction equation

HRID 1294545 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[O:10][CH3:11].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:31]([OH:35])[CH2:32][C:33]#[CH:34]>C(NCC)C.[Pd](Cl)Cl.[Cu]I>[CH3:11][O:10][C:3]1[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=1[C:34]#[C:33][CH2:32][CH2:31][OH:35]

Participants

7

Reactant 3

HCID 11776TriphenylphosphineHCID 135663-Butyn-1-OLHCID 872661-Bromo-2,4-dimethoxybenzene

Product 1

HCID 225661274-(2,4-Dimethoxyphenyl)-but-3-yn-1-olYield 44.3%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8021DiethylamineSolvent

Conditions

Temperature
55 °C

Procedure

1-Bromo-2,4-dimethoxybenzene (10 g 0.046 mol), palladium chloride (0.2 g 0.11 mmol) and triphenylphosphine (0.6 g 0.0023 mol) were dissolved in diethylamine (100 mL) under a nitrogen atmosphere. Copper (I) iodide (0.44 g 0.0023 mol) and 3-butyn-1-ol (7 mL 0.092 mol) were added into the reaction mixture at once. The mixture was stirred overnight at 55° C. under a nitrogen atmosphere. The catalyst was filtered off from the reaction mixture and the same amount of palladium chloride, triphenylphosphine, copper (I) iodide and 3-butyn-1-ol were added. The reaction mixture was stirred and heated at 85° C. for 48 hours. Then the solvent was removed at reduced pressure and water (approx. 100 mL) was added to the residue. The mixture was extracted with ethyl acetate (350 mL) passed through a pad of silica gel and concentrated. The product was purified by flash chromatography (silica gel, 1:1 hexanes/ethyl acetate). Compound 75 (4.2 g, 24%) was isolated as a brown oil. 1H NMR (300 MHz, CDCl3) δ 2.24 (t, 1H), 2.73 (t, 2H), 3.80 (br s, 5H), 3.87 (s, 3H), 6.43 (m, 2H), 7.30 (m, 1H).

Workup

  1. filtrationThe catalyst was filtered off from the reaction mixture
  2. additionthe same amount of palladium chloride, triphenylphosphine, copper (I) iodide and 3-butyn-1-ol were added
  3. stirringThe reaction mixture was stirred
  4. temperatureheated at 85° C. for 48 hours
  5. customThen the solvent was removed at reduced pressure and water (approx. 100 mL)
  6. additionwas added to the residue
  7. extractionThe mixture was extracted with ethyl acetate (350 mL)
  8. concentrationconcentrated
  9. customThe product was purified by flash chromatography (silica gel, 1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-be44cc316c364e9ea4198227d2787e2f
Source dataset
uspto-grants-2007_07
Patent number
US07241766B2

Reaction notes

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