Ethylenediamine → Methyl 5-cyano-2-hydroxybenzoate

HRID 1291003Notes

Reaction equation

HRID 1291003 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([OH:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[Cu][C:14]#[N:15].CN1CCCC1=O.C(N)CN>S([O-])([O-])(=O)=O.[Cu+2].O>[C:14]([C:2]1[CH:3]=[CH:4][C:5]([OH:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])#[N:15]

Participants

7

Reactant 4

HCID 3301EthylenediamineHCID 13387N-methyl-2-pyrrolidoneHCID 77683Methyl 5-bromosalicylateHCID 178418546HCID 178418546, compound

Product 1

HCID 10583428Methyl 5-cyano-2-hydroxybenzoateYield 15%

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 962WaterSolvent

Procedure

Methyl 5-bromo-2-hydroxybenzoate (25.6 g, 129 mmol), copper(I) cyanide (20.8 g, 257 mmol) and copper sulfate (200 mg) were added to N-methyl-2-pyrrolidone (250 ml) and the mixture was refluxed under heating for 2 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and poured into a mixture of water (500 ml) and ethylenediamine (10 ml). After filtration, the filtrate was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After filtration, low boiling matters were distilled away from the filtrate under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=5/1) to give 3.35 g of methyl 5-cyano-2-hydroxybenzoate as a colorless solid (15%). This solid (3.35 g, 18.9 mmol) and potassium carbonate (5.23 g, 37.0 mmol) were added to N,N-dimethylformamide (45 ml), and ethyl bromoacetate (2.21 ml, 19.9 mmol) was gradually added, which was followed by stirring at room temperature for 18 hours. Water was added to the reaction mixture and the mixture was extracted with an equivalent mixture of ethyl acetate and n-hexane. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After filtration, low boiling matters were distilled away from the filtrate under reduced pressure to give a crude product of ethyl 4-cyano-2-methoxycarbonylphenoxyacetate. This product (3.39 g, 19.3 mol) was dissolved in ethanol (20 ml) and the obtained solution was gradually added to a solution of metallic sodium (622 mg, 27.1 mmol) dissolved in ethanol (50 ml). The mixture was stirred at room temperature for 45 minutes. Low boiling matters were distilled away from the reaction mixture under reduced pressure and water (200 ml) was added to the residue. Dilute hydrochloric acid was added to adjust the pH to 2-3. The resulting precipitate was collected by filtration to quantitatively give 2.98 g of ethyl 5-cyano-3-hydroxy-2-benzofurancarboxylate as a colorless solid.

Workup

  1. temperaturethe mixture was refluxed
  2. temperatureunder heating for 2 hours under a nitrogen atmosphere
  3. filtrationAfter filtration
  4. extractionthe filtrate was extracted with ethyl acetate
  5. washThe extract was washed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationAfter filtration, low boiling matters
  8. distillationwere distilled away from the filtrate under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=5/1)

Sources & evidence

ORD record
ord-ef52f1fdc9d74dbdab5b8433aed5b82b
Source dataset
uspto-grants-1998_05
Patent number
US05753670

Reaction notes

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