Methyl chloroacetate → 7-Bromobenzofuran-2-carboxylic acid

HRID 335569Notes

Reaction equation

HRID 335569 reaction equation
[Br:1][C:2]1[C:3]([OH:10])=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=O.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:18][C:19]([O:21]C)=[O:20].[OH-].[K+]>O.C1COCC1>[Br:1][C:2]1[C:3]2[O:10][C:18]([C:19]([OH:21])=[O:20])=[CH:5][C:4]=2[CH:7]=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 7295Methyl chloroacetateHCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 109105553-Bromo-2-hydroxybenzaldehyde

Product 1

HCID 179826517-Bromobenzofuran-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
130 °C

Procedure

10 g (49.75 mmol) of 3-bromo-2-hydroxybenzaldehyde and 1.84 g (4.97 mmol) of tetra-N-butylammonium iodide are, together with 27.5 g (199.0 mmol) of anhydrous potassium carbonate, initially charged. 24.3 g (223.86 mmol) of methyl chloroacetate are added. The reaction mixture is heated at 130° C. for 4 h and then cooled to 0° C. using an ice bath. 100 ml of THF and 16.75 g (298.5 mmol) of potassium hydroxide in 100 ml of water are added, the mixture is then stirred at 40° C. for 4 h. The solvent is removed under reduced pressure. The residue is diluted with water and acidified with conc. hydrochloric acid. The product is purified on silica gel 60 (mobile phase: toluene/ethyl acetate/acetic acid 40:10:1). The solvent is removed under reduced pressure. Any last solvent residues are finally removed under high vacuum. Fine purification is carried out by preparative HPLC. 303 mg (2.5% of theory) of the title compound are isolated.

Workup

  1. additioninitially charged
  2. temperaturecooled to 0° C.
  3. customThe solvent is removed under reduced pressure
  4. additionThe residue is diluted with water
  5. customThe product is purified on silica gel 60 (mobile phase: toluene/ethyl acetate/acetic acid 40:10:1)
  6. customThe solvent is removed under reduced pressure
  7. customAny last solvent residues are finally removed under high vacuum
  8. customFine purification

Sources & evidence

ORD record
ord-f3bef1074feb44129b07dad8f797a217
Source dataset
uspto-grants-2014_11
Patent number
US08884017B2

Reaction notes

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