Hydrochloric Acid → 3-[2-(4-Carbamoylphenyl)ethyl]-4-hydroxybenzofuran

HRID 230917Notes

Reaction equation

HRID 230917 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12]2[C:16]3[C:17]([OH:21])=[CH:18][CH:19]=[CH:20][C:15]=3[O:14][CH:13]=2)=[CH:6][CH:5]=1)(O)=[O:2].C(=O)([O-])O.[NH4+:26].C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.Cl>CN(C)C=O.N1C=CC=CC=1>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12]2[C:16]3[C:17]([OH:21])=[CH:18][CH:19]=[CH:20][C:15]=3[O:14][CH:13]=2)=[CH:6][CH:5]=1)(=[O:2])[NH2:26]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14013Ammonium BicarbonateHCID 90495Di-tert-butyl dicarbonateHCID 67136040HCID 67136040, compound

Product 1

HCID 671358783-[2-(4-Carbamoylphenyl)ethyl]-4-hydroxybenzofuranYield 62.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-[2-(4-carboxyphenyl)ethyl]-4-hydroxybenzofuran (80 mg), ammonium hydrogen carbonate (90 mg) and pyridine (0.091 mL) in N,N-dimethylformamide (3 mL) was added ditert-butyl dicarbonate (0.25 g), and the mixture was stirred at room temperature overnight. To the reaction mixture was added 0.5 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water, a saturated aqueous sodium hydrogen carbonate solution and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in methanol (5 mL). To the solution was added sodium methoxide (28% methanol solution, 0.1 mL), and the mixture was stirred at 50° C. for 3 hours. The reaction mixture was cooled to room temperature. To the mixture was added 1 mol/L hydrochloric acid (0.52 mL), and the resulting mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=30/1) and VARIAN BOND ELUT-SAX (eluent: methanol) successively to give the title compound (50 mg).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with water
  3. dry with materiala saturated aqueous sodium hydrogen carbonate solution and brine successively, and dried over anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. dissolutionthe residue was dissolved in methanol (5 mL)
  6. additionTo the solution was added sodium methoxide (28% methanol solution, 0.1 mL)
  7. stirringthe mixture was stirred at 50° C. for 3 hours
  8. temperatureThe reaction mixture was cooled to room temperature
  9. additionTo the mixture was added 1 mol/L hydrochloric acid (0.52 mL)
  10. concentrationthe resulting mixture was concentrated under reduced pressure
  11. customthe residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=30/1) and VARIAN BOND ELUT-SAX (eluent: methanol) successively

Sources & evidence

ORD record
ord-f6e697f52f19467793ab7d99c5c68fdc
Source dataset
uspto-grants-2009_07
Patent number
US07566699B2

Reaction notes

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