Ethanol → 4-bromo-3-ethoxymethyl-benzoic acid ethyl ester

HRID 219836Notes

Reaction equation

HRID 219836 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10]C(C(OC)=O)=[CH:4][C:3]=1[CH2:12][O:13][CH3:14].C[O:16][CH2:17][C:18]1C=C(C(O)=O)C=CC=1C1C=CC=CC=1C.[CH3:34][CH2:35][O-:36].[Na+].[CH3:38]CO>>[Br:1][C:2]1[CH:11]=[CH:10][C:34]([C:35]([O:16][CH2:17][CH3:18])=[O:36])=[CH:4][C:3]=1[CH2:12][O:13][CH2:14][CH3:38]

Participants

5

Reactant 4

HCID 702EthanolHCID 2723922Sodium ethoxideHCID 58554220Methyl 4-bromo-3-(methoxymethyl)benzoateHCID 594958222-(Methoxymethyl)-2'-methylbiphenyl-4-carboxylic acid

Product 1

HCID 225746704-bromo-3-ethoxymethyl-benzoic acid ethyl ester

Conditions

Temperature
80 °C

Procedure

To a solution of methyl 4-bromo-3-(bromomethyl)benzoate (Intermediate 28, Step 1), (2.50 g; 8.12 mmol; 1 eq.) in EtOH (12.50 mL) was added sodium ethylate (1 104.83 mg; 16.24 mmol; 2 eq.) and the mixture was stirred overnight at 80° C. After evaporation of the solvent, the mixture was partitioned between EtOAc and water. The organic layer was washed with a 5% NaHCO3 aqueous solution, NaCl sat. solution, dried over magnesium sulfate, filtered off and dried under vacuum to afford a yellow oil. Purification by flash chromatography (cHex/ethyle acetate) afforded the title compound as a yellow oil. 1H NMR (CDCl3) δ 8.13 (d, J=2.1 Hz, 1H), 7.80 (dd, J=8.3, 2.1 Hz, 1H), 7.61 (d, J=8.3 Hz, 1H), 4.58 (s, 2H), 4.38 (q, J=7.2 Hz, 2H), 3.64 (q, J=7.0 Hz, 2H), 1.39 (t, J=7.2 Hz, 3H), 1.30 (t, J=7.0 Hz, 3H). LC/MS (Method B): 382.2 ((M−H)+ACN)−; 330.2 ((M+H)+ACN)+. HPLC (Method A), Rt 4.90 min (purity: 78.5%).

Workup

  1. customAfter evaporation of the solvent
  2. customthe mixture was partitioned between EtOAc and water
  3. washThe organic layer was washed with a 5% NaHCO3 aqueous solution, NaCl sat. solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered off
  6. customdried under vacuum
  7. customto afford a yellow oil
  8. customPurification by flash chromatography (cHex/ethyle acetate)

Sources & evidence

ORD record
ord-ea001b51058b471c9aff281968e09268
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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