Bromine → 2-Bromo-5-[2-(3-chloro-phenyl)-ethoxy]-4-methoxy-benzoic acid methyl ester

HRID 2094683Notes

Reaction equation

HRID 2094683 reaction equation
OC1C=C(C=CC=1OC)C(OC)=O.ClC1C=C(CCO)C=CC=1.[CH3:24][O:25][C:26](=[O:45])[C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[C:29]([O:35][CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=2)[CH:28]=1.C([O-])(=O)C.[Na+].[Br:51]Br>C(O)(=O)C>[CH3:24][O:25][C:26](=[O:45])[C:27]1[CH:28]=[C:29]([O:35][CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=2)[C:30]([O:33][CH3:34])=[CH:31][C:32]=1[Br:51]

Participants

7

Reactant 5

HCID 24408Bromine2×HCID 78856m-Chlorophenethylic alcoholHCID 517045Sodium AcetateHCID 4056967Methyl 3-hydroxy-4-methoxybenzoateHCID 670762963-[2-(3-Chloro-phenyl)-ethoxy]-4-methoxy-benzoic acid methyl ester

Product 1

HCID 670764442-Bromo-5-[2-(3-chloro-phenyl)-ethoxy]-4-methoxy-benzoic acid methyl esterYield 48.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
95 °C

Procedure

Methyl 3-hydroxy-4-methoxybenzoate and 2-(3-chlorophenyl)-ethanol were reacted in analogy to step 1 of example 1. The obtained 3-[2-(3-chloro-phenyl)-ethoxy]-4-methoxy-benzoic acid methyl ester (300 mg, 0.935 mmol) and sodium acetate (230 mg, 2.81 mmol) were dissolved in acetic acid (10 ml), bromine (224 mg, 1.40 mmol) was added, and the mixture was stirred at 95° C. with reaction control every hour. When the reaction did no more proceed, further bromine was added. After 5 h the reaction was completed. The volatiles were evaporated in vacuo, the residue was partitioned between EA and a saturated aqueous sodium hydrogencarbonate solution, and the aqueous phase extracted with EA. The combined organic extracts were washed with a saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated to dryness. This residue was purified by silica chromatography (HEP/EA gradient) to give 180 mg of the title compound.

Workup

  1. customThe volatiles were evaporated in vacuo
  2. customthe residue was partitioned between EA
  3. extractiona saturated aqueous sodium hydrogencarbonate solution, and the aqueous phase extracted with EA
  4. washThe combined organic extracts were washed with a saturated sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThis residue was purified by silica chromatography (HEP/EA gradient)

Sources & evidence

ORD record
ord-4b61be606a4244a4b2498c85e402f322
Source dataset
uspto-grants-2013_05
Patent number
US08445530B2

Reaction notes

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