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

HRID 579302Notes

Reaction equation

HRID 579302 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.C(Cl)Cl>[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

8

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 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

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, then dried over magnesium sulfate and concentrated to provide an orange solid. The solid was suspended in DCM (200 mL) and stirred overnight. The solid (primarily unreacted 4-bromo-3,5-dihydroxybenzoate) was removed by filtration and the filtrate was concentrated to provide 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
  5. customto provide an orange solid
  6. stirringstirred overnight
  7. customThe solid (primarily unreacted 4-bromo-3,5-dihydroxybenzoate) was removed by filtration
  8. concentrationthe filtrate was concentrated
  9. customto provide an orange oil which
  10. customwas purified by column chromatography (80 g silica gel, 2:1 DCM in heptane elution, followed by DCM elution)

Sources & evidence

ORD record
ord-d5cceaebbf624164ac2716079674fcb6
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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