Cesium carbonate → Methyl 3-(hydroxymethyl)-5-methylbenzoate

HRID 348914Notes

Reaction equation

HRID 348914 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH2:12][OH:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:14](=O)([O-])[O-].[Cs+].[Cs+].C(=O)([O-])[O-].[K+].[K+].CB1OB(C)OB(C)O1>O1CCOCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[OH:13][CH2:12][C:10]1[CH:9]=[C:4]([CH:3]=[C:2]([CH3:14])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 11356988Methyl 3-bromo-5-(hydroxymethyl)benzoate

Product 1

HCID 21086184Methyl 3-(hydroxymethyl)-5-methylbenzoate

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of methyl 3-bromo-5-(hydroxymethyl)benzoate (4.53 g, 18.5 mmol) in dioxane (74 mL) is added cesium carbonate (6.0 g, 18.5 mmol), potassium carbonate (5.1 g, 37 mmol), and palladium(0) tetrakis(triphenylphosphine) (2.1 g, 1.85 mmol), followed by trimethyl boroxine (5.1 mL, 37 mmol). The reaction mixture is refluxed for 12 h, cooled to room temperature, and then partitioned between water and ethyl acetate. The organic layer is washed with water and brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. The black oil is adsorbed onto silica gel followed by purification by flash column chromatography (silica, 25% ethyl acetate/hexanes) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ 7.75 (s, 1H), 7.65 (s, 1H), 7.39 (s, 1H), 5.31 (br s, 1H), 4.53 (s, 1H), 3.84 (s, 3H), 2.36 (s, 3H).

Workup

  1. temperatureThe reaction mixture is refluxed for 12 h
  2. custompartitioned between water and ethyl acetate
  3. washThe organic layer is washed with water and brine
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customfollowed by purification by flash column chromatography (silica, 25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9ec7bfbd9240402b98e663c0b4ff423d
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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