Hydrochloric Acid → Methyl 3-(benzyloxy)-4-bromo-5-hydroxybenzoate

HRID 1027206Notes

Reaction equation

HRID 1027206 reaction equation
[Br:1][C:2]1[C:11]([OH:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[OH:13].C(=O)([O-])[O-].[K+].[K+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl>CN(C=O)C.O>[CH2:20]([O:12][C:11]1[CH:10]=[C:5]([CH:4]=[C:3]([OH:13])[C:2]=1[Br:1])[C:6]([O:8][CH3:9])=[O:7])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 118602Benzoic acid, 4-bromo-3,5-dihydroxy-, methyl ester

Product 1

HCID 86710603Methyl 3-(benzyloxy)-4-bromo-5-hydroxybenzoateYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of methyl 4-bromo-3,5-dihydroxybenzoate (18.8 g, 76 mmol) and potassium carbonate (5.26 g, 38.1 mmol) in DMF (190 mL) was added benzyl bromide (3.17 mL, 26.6 mmol). The mixture was stirred overnight, diluted with 200 mL water and acidified to pH 1 by slow addition of concentrated hydrochloric acid. The solution was extracted with 1:1 ethyl acetate/ether (6×) and the combined extracts were washed with water (8×), saturated sodium bicarbonate, brine, dried over magnesium sulfate and concentrated to an orange solid. The solids were suspended in DCM (200 mL) and stirred overnight. The solids (primarily unreacted 4-bromo-3,5-dihydroxybenzoate) were removed by filtration and the filtrate was concentrated to an orange oil which was purified by column chromatography (80 g silica gel, 2:1 DCM in heptane elution, followed by DCM elution) to provide methyl 3-(benzyloxy)-4-bromo-5-hydroxybenzoate (4.66 g). MS (M+1)=337.0. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.32-7.57 (m, 6H), 7.26 (d, J=1.52 Hz, 1H), 5.77 (s, 1H), 5.22 (s, 2H), 3.93 (s, 3H) as well as the di-benzylated methyl 3,5-bis(benzyloxy)-4-bromobenzoate (1.8 g).

Workup

  1. extractionThe solution was extracted with 1:1 ethyl acetate/ether (6×)
  2. washthe combined extracts were washed with water (8×), saturated sodium bicarbonate, brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated to an orange solid
  5. stirringstirred overnight
  6. customThe solids (primarily unreacted 4-bromo-3,5-dihydroxybenzoate) were removed by filtration
  7. concentrationthe filtrate was concentrated to an orange oil which
  8. customwas purified by column chromatography (80 g silica gel, 2:1 DCM in heptane elution, followed by DCM elution)

Sources & evidence

ORD record
ord-121a17ddbacd455fa589187baed34146
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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