Potassium Carbonate → 3-(3-Hydroxy-propoxy)-4-methoxy-benzoic acid methyl ester

HRID 1158445Notes

Reaction equation

HRID 1158445 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:5]([O:7][CH3:8])=[O:6].Br[CH2:15][CH2:16][CH2:17][OH:18].C([O-])([O-])=O.[K+].[K+].CCCCCC.CCOC(C)=O>CC#N>[CH3:8][O:7][C:5](=[O:6])[C:4]1[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:2]([O:1][CH2:15][CH2:16][CH2:17][OH:18])[CH:3]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 123083-Bromo-1-propanolHCID 4056967Methyl 3-hydroxy-4-methoxybenzoateHCID 21226206Ethyl acetate hexane

Product 1

HCID 686170883-(3-Hydroxy-propoxy)-4-methoxy-benzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of methyl 3-hydroxy-4-methoxybenzoate (4.94 g, 26.6 mmol), 3-bromo-1-propanol (2.86 mL, 31.9 mmol) and anhydrous K2CO3 (5.51 g, 39.9 mmol) in MeCN (50 mL) is refluxed with stirring overnight, and after cooling is poured into ice/water. The aqueous layer is extracted with AcOEt, and the combined organics are washed with brine, dried (Na2SO4) and concentrated. Purification by flash chromatography on silica gel (hexane/AcOEt 1:2) gives a solid residue which is stirred in a 9:1 mixture of hexane/AcOEt over 30 min. Filtration of the suspension and drying in vacuo gives the title compound as white solid. TLC, Rf (hexane/AcOEt 1:1)=0.09. MS: 241.2 [M+H]+. tR (HPLC, Nucleosil C18HD column, 20-100% CH3CN/H2O/6 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 2.86 min. 1H-NMR (CDCl3): δ 2.13 (m, 2H), 2.59 (m, 1H), 3.92 (s, 3H), 3.93 (s, 3H), 4.29 (m, 2H), 6.92 (m, 1H), 7.60 (s, 1H), 7.73 (m, 1H) ppm.

Workup

  1. temperatureis refluxed
  2. temperatureafter cooling
  3. extractionThe aqueous layer is extracted with AcOEt
  4. washthe combined organics are washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification by flash chromatography on silica gel (hexane/AcOEt 1:2)
  8. customgives a solid residue which
  9. filtrationFiltration of the suspension
  10. customdrying in vacuo

Sources & evidence

ORD record
ord-dbd03fa395df4f3a9ad76b10cc9c1a97
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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