Acetic Acid → HCID 22666383, compound

HRID 1007940Notes

Reaction equation

HRID 1007940 reaction equation
[F:1][C:2]1[C:3]([C:13](O)=O)=[CH:4][C:5]2[CH:9]=[CH:8][S:7][C:6]=2[C:10]=1[O:11][CH3:12].S(Cl)(Cl)=O.[C:20]([OH:23])(=[O:22])C.Cl.[CH2:25](Cl)Cl>C(OCC)(=O)C.O>[F:1][C:2]1[C:3]([CH2:13][C:20]([O:23][CH3:25])=[O:22])=[CH:4][C:5]2[CH:9]=[CH:8][S:7][C:6]=2[C:10]=1[O:11][CH3:12]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 24386Thionyl ChlorideHCID 22666264HCID 22666264, compound

Product 1

HCID 22666383HCID 22666383, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

In 40 mL of methylene chloride is suspended 4.00 g of 6-fluoro-7-methoxybenzo[b]thiophene-5-carboxylic acid, to which is added 1.55 mL of thionyl chloride. The mixture is heated under reflux for 2 hours. The reaction mixture is concentrated under reduced pressure, and the residue is dissolved in 40 mL of methylene chloride. At an ice-cooled temperature, 200 mL of 0.5 mol/L solution of diazomethane in diethyl ether is added to the solution obtained above, and the mixture thus formed is stirred at ambient temperature for one hour. Then, 6.1 mL of acetic acid is added to the reaction mixture, and the mixture is stirred at ambient temperature for 10 minutes. Then, water and ethyl acetate are added, and the organic layer is separated. The organic layer is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue is suspended in 40 mL of methanol, a mixture of 2.03 g of silver benzoate and 17.3 mL of triethylamine is added at 5° C., and the mixture thus formed is stirred at ambient temperature for one hour. Water and ethyl acetate are added to the reaction mixture, pH is adjusted to 1 with 6 mol/L hydrochloric acid, the insoluble matter is filtered off, and the organic layer is separated. The organic layer is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, the solvent is distilled off under reduced pressure, and the residue thus obtained is purified by column chromatography (eluent: hexane:ethyl acetate=5:1) to obtain 3.87 g of methyl 2-(6-fluoro-7-methoxybenzo[b]thiophen-5-yl)-acetate.

Workup

  1. temperatureThe mixture is heated
  2. temperatureunder reflux for 2 hours
  3. concentrationThe reaction mixture is concentrated under reduced pressure
  4. dissolutionthe residue is dissolved in 40 mL of methylene chloride
  5. temperatureAt an ice-cooled temperature, 200 mL of 0.5 mol/L solution of diazomethane in diethyl ether
  6. additionis added to the solution
  7. customobtained above, and the mixture
  8. customthus formed
  9. stirringthe mixture is stirred at ambient temperature for 10 minutes
  10. customthe organic layer is separated
  11. washThe organic layer is washed with saturated aqueous solution of sodium chloride
  12. dry with materialdried over anhydrous magnesium sulfate
  13. distillationthe solvent is distilled off under reduced pressure
  14. additiona mixture of 2.03 g of silver benzoate and 17.3 mL of triethylamine
  15. additionis added at 5° C.
  16. customthe mixture thus formed
  17. stirringis stirred at ambient temperature for one hour
  18. filtrationthe insoluble matter is filtered off
  19. customthe organic layer is separated
  20. washThe organic layer is washed with saturated aqueous solution of sodium chloride
  21. dry with materialdried over anhydrous magnesium sulfate
  22. distillationthe solvent is distilled off under reduced pressure
  23. customthe residue thus obtained
  24. customis purified by column chromatography (eluent: hexane:ethyl acetate=5:1)

Sources & evidence

ORD record
ord-3a686dca9a514a01993c8348e6230f98
Source dataset
uspto-grants-2004_09
Patent number
US06797726B1

Reaction notes

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