Propargyl alcohol → 5-Benzyloxy-2-(3-hydroxy-prop-1-ynyl)-benzoic acid methyl ester

HRID 572487Notes

Reaction equation

HRID 572487 reaction equation
[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:7]=[CH:6][C:5]=1Br.[CH2:20]([OH:23])[C:21]#[CH:22]>C(N(CC)CC)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>[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:7]=[CH:6][C:5]=1[C:22]#[C:21][CH2:20][OH:23]

Participants

6

Reactant 2

HCID 7859Propargyl alcoholHCID 66726186HCID 66726186, compound

Product 1

HCID 682958095-Benzyloxy-2-(3-hydroxy-prop-1-ynyl)-benzoic acid methyl esterYield 72.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 5-Benzyloxy-2-bromo-benzoic acid methyl ester (120 g, 374 mmol) and prop-2-yn-1-ol (41.9 g, 747 mmol) in triethylamine (1 L), copper(I) iodide (0.712 g, 3.74 mmol) and bis(triphenylphosphine)palladium(II) chloride (26.2 g, 37.4 mmol) at RT under N2. The mixture was heated at 50° C. reflux under N2 for 12 hr. The reaction was cooled to room temperature, concentrated to dryness, diluted with H2O (50 mL) and extracted with ethyl acetate (500 mL*3), The organic phase was washed with saturated sodium bicarbonate solution 500 mL, dried over Na2SO4. After concentration, the crude product was purified by silica gel chromatography eluted with PE:EA=10:1˜4:1 to give title product (80 g, 72%) as yellow oil.

Workup

  1. customat RT
  2. temperaturereflux under N2 for 12 hr
  3. temperatureThe reaction was cooled to room temperature
  4. concentrationconcentrated to dryness
  5. additiondiluted with H2O (50 mL)
  6. extractionextracted with ethyl acetate (500 mL*3)
  7. washThe organic phase was washed with saturated sodium bicarbonate solution 500 mL
  8. dry with materialdried over Na2SO4
  9. concentrationAfter concentration
  10. customthe crude product was purified by silica gel chromatography
  11. washeluted with PE

Sources & evidence

ORD record
ord-b874bf18c8574716b140a07c6e949398
Source dataset
uspto-grants-2015_05
Patent number
US09029391B2

Reaction notes

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