Water → HCID 22666329, compound

HRID 1007950Notes

Reaction equation

HRID 1007950 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[C:7]([F:24])=[CH:8][C:9]2[C:13](=O)[CH:12](C(OC(C)(C)C)=O)[S:11][C:10]=2[C:22]=1[F:23])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O.B.[Na]>C1(C)C=CC=CC=1.CO>[F:24][C:7]1[C:6]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:25])=[C:22]([F:23])[C:10]2[S:11][CH:12]=[CH:13][C:9]=2[CH:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 521998p-Toluenesulfonic acid monohydrate2×HCID 22666364HCID 22666364, compoundHCID 178418435HCID 178418435, compound

Product 1

HCID 22666329HCID 22666329, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

In 60 mL of toluene is dissolved 19.2 g of tert-butyl 6-(2-ethoxy-2-oxoethyl)-5,7-difluoro-3-oxo-2,3-dihydrobenzo[b]thiophene-2-carboxylate, to which is added 0.96 g of p-toluenesulfonic acid monohydrate. The mixture is heated under reflux for 2.5 hours. Water is added to the reaction mixture, and the organic layer is separated. The organic layer is washed with water, saturated aqueous solution of sodium bicarbonate and saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue thus obtained is dissolved in 100 ml of methanol, 0.97 g of sodium boron hydride is added, and the mixture thus formed is stirred at ambient temperature for 30 minutes. Then, 5.88 g of p-toluenesulfonic acid monohydrate is added and the mixture thus formed is heated under reflux for one hour. The reaction mixture is concentrated under reduced pressure, water and ethyl acetate are added to the residue, and the organic layer is separated. The organic layer is washed with water, saturated aqueous solution of sodium bicarbonate and saturated aqueous solution of sodium chloride successively and dried over anhydrous magnesium sulfate, the solvent is distilled off under reduced pressure, and the residue is purified by column chromatography (eluent: hexane:ethyl acetate=50:1 to 20:1) to obtain 1.98 g of ethyl 2-(5,7-difluorobenzo[b]thiophen-6-yl)acetate as an oily product.

Workup

  1. temperatureThe mixture is heated
  2. temperatureunder reflux for 2.5 hours
  3. customthe organic layer is separated
  4. washThe organic layer is washed with water, saturated aqueous solution of sodium bicarbonate and saturated aqueous solution of sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent is distilled off under reduced pressure
  7. customThe residue thus obtained
  8. customthe mixture thus formed
  9. customthe mixture thus formed
  10. temperatureis heated
  11. temperatureunder reflux for one hour
  12. concentrationThe reaction mixture is concentrated under reduced pressure, water and ethyl acetate
  13. additionare added to the residue
  14. customthe organic layer is separated
  15. washThe organic layer is washed with water, saturated aqueous solution of sodium bicarbonate and saturated aqueous solution of sodium chloride successively
  16. dry with materialdried over anhydrous magnesium sulfate
  17. distillationthe solvent is distilled off under reduced pressure
  18. customthe residue is purified by column chromatography (eluent: hexane:ethyl acetate=50:1 to 20:1)

Sources & evidence

ORD record
ord-9f25db03a7c94e9eb1c95871b253a71d
Source dataset
uspto-grants-2004_09
Patent number
US06797726B1

Reaction notes

Loading…