Methanol → Methyl 5-bromo-2-hydroxy-3-methoxybenzoate

HRID 217161Notes

Reaction equation

HRID 217161 reaction equation
S(=O)(=O)(O)O.[Br:6][C:7]1[CH:8]=[C:9]([O:17][CH3:18])[C:10]([OH:16])=[C:11]([CH:15]=1)[C:12]([OH:14])=[O:13].CO.[C:21](OCC)(=O)C>CCCCCC>[CH3:21][O:13][C:12](=[O:14])[C:11]1[CH:15]=[C:7]([Br:6])[CH:8]=[C:9]([O:17][CH3:18])[C:10]=1[OH:16]

Participants

6

Reactant 4

HCID 887MethanolHCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 135960815-Bromo-2-hydroxy-3-methoxybenzoic acid

Product 1

HCID 15054916Methyl 5-bromo-2-hydroxy-3-methoxybenzoate

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

To prepare this compound, initially 1.0 mL of 98% concentrated sulfuric acid was added to a solution of 5-bromo-2-hydroxy-3-methoxy-benzoic acid, (compound 6) (1.0 g, 4.0 mmol) in 50 of methanol. The reaction mixture was refluxed overnight until thin layer chromatography using 20% ethyl acetate and 80% hexane as the mobile phase indicated that the reaction was complete. After evaporating the methanol, the residue was dissolved in 60 mL of ethyl acetate and washed with a saturated NaHCO3 aqueous solution and then brine. After drying with anhydrous sodium sulfate, the solution was concentrated, and the crude product was purified on a silica gel column to isolate the intermediate, 5-bromo-2-hydroxy-3-methoxy-benzoic acid methyl ester. The yield of this intermediate was 94%. The 1H-NMR spectrum (300 MHz, CDCl3) of the purified product was: 3.88 (s 3H), 3.95 (s, 3H), 7.09 (d, 1H), 7.55 (t, 1H), 10.96 (d, 1H).

Workup

  1. temperatureThe reaction mixture was refluxed overnight until thin layer chromatography
  2. customAfter evaporating the methanol
  3. dissolutionthe residue was dissolved in 60 mL of ethyl acetate
  4. washwashed with a saturated NaHCO3 aqueous solution
  5. dry with materialAfter drying with anhydrous sodium sulfate
  6. concentrationthe solution was concentrated
  7. customthe crude product was purified on a silica gel column

Sources & evidence

ORD record
ord-7adde2b85aaa438a8a96941ba9d487fd
Source dataset
uspto-grants-2012_06
Patent number
US08193360B2

Reaction notes

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