o-Xylyl bromide → Methyl 3-hydroxy-5-{[(2-methylphenyl)methyl]oxy}benzoate

HRID 1373173Notes

Reaction equation

HRID 1373173 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([OH:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[H-].[Na+].[CH3:15][C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[CH2:18]Br>CN(C)C=O>[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH2:15][C:16]2[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=2[CH3:18])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

5

Reactant 3

HCID 6992o-Xylyl bromideHCID 24758Sodium hydrideHCID 75076Methyl 3,5-Dihydroxybenzoate

Product 1

HCID 21074227Methyl 3-hydroxy-5-{[(2-methylphenyl)methyl]oxy}benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
15 °C

Procedure

To a solution of methyl 3,5-dihydroxybenzoate (50 g, 0.30M) in N,N-dimethylformamide (500 ml) at 0° C. was added sodium hydride (10.8 g, 0.27M) portionwise, maintaining the reaction temperature below 10° C. The reaction was allowed to warm to 15° C. and was stirred for 20 minutes. The mixture was cooled to 0° C. and a solution of 2-methylbenzyl bromide (36 ml, 0.27M) in N,N-dimethylformamide (50 ml) was added over 30 minutes. The reaction was warmed to ambient temperature and concentrated ‘in vacuo’. Ethyl acetate (500 ml) was added to the residue and the resulting organic solution was washed first with water (2×250 ml) and then with a saturated aqueous sodium chloride solution (200 ml). The organic layer was dried with magnesium sulfate and then concentrated ‘in vacuo’. The crude product was chromatographed on Kieselgel 60, eluting with a gradient of 0–100% ethyl acetate in iso-hexane to give methyl 3-hydroxy-5-(2-methylbenzyloxy)-benzoate as a colourless solid (21.9 g); H1 NMR δ (d6-DMSO) 2.39 (3H s) 3.90 (3H s) 5.02 (2H s) 5.61 (1H s) 6.69 (1H t) 7.15–7.42 (6H, m). MS [MH]+ 488

Workup

  1. temperaturemaintaining the reaction temperature below 10° C
  2. temperatureThe mixture was cooled to 0° C.
  3. temperatureThe reaction was warmed to ambient temperature
  4. concentrationconcentrated ‘in vacuo’
  5. additionEthyl acetate (500 ml) was added to the residue
  6. washthe resulting organic solution was washed first with water (2×250 ml)
  7. dry with materialThe organic layer was dried with magnesium sulfate
  8. concentrationconcentrated ‘in vacuo’
  9. customThe crude product was chromatographed on Kieselgel 60
  10. washeluting with a gradient of 0–100% ethyl acetate in iso-hexane

Sources & evidence

ORD record
ord-010c2d2a131647148b2d00e158d25f7f
Source dataset
uspto-grants-2007_01
Patent number
US07160906B2

Reaction notes

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