Methyl chloroacetate → 6-Bromo-1-benzofuran-2-carboxylic acid

HRID 335570

Reaction equation

HRID 335570 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([OH:10])[CH:3]=1.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[CH:9]=[CH:8][C:5]2[CH:6]=[C:18]([C:19]([OH:21])=[O:20])[O:10][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 7295Methyl chloroacetateHCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 40660194-Bromo-2-hydroxybenzaldehyde

Product 1

HCID 14744716-Bromo-1-benzofuran-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
130 °C

Procedure

8.0 g (39.8 mmol) of 4-bromo-2-hydroxybenzaldehyde and 1.47 g (3.98 mmol) of tetra-N-butylammonium iodide are, together with 22 g (159.19 mmol) of anhydrous potassium carbonate, initially charged. 9.07 g (83.57 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 13.4 g (238.8 mmol) of potassium hydroxide in 50 ml of water are added and the mixture is then stirred at RT overnight. The solvent is removed under reduced pressure. The residue is diluted with water and acidified with conc. hydrochloric acid. The product is filtered off and dried under high vacuum. For fine purification, the product is purified on silica gel 60 (mobile phase: toluene→toluene/acetic acid 50:1→toluene/ethyl acetate/acetic acid 35:5:1). The solvent is removed under reduced pressure. 3.8 g (40% 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. filtrationThe product is filtered off
  6. customdried under high vacuum
  7. customFor fine purification
  8. customthe product is purified on silica gel 60 (mobile phase: toluene→toluene/acetic acid 50:1→toluene/ethyl acetate/acetic acid 35:5:1)
  9. customThe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-d481d67b95e24c65b04b403afcf8869e
Source dataset
uspto-grants-2014_11
Patent number
US08884017B2

Linked notes

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