Acetic Anhydride → Ethyl 3-(1-acetyl-pyrrolidin-2-yl)-4-hydroxybenzoate

HRID 13262Notes

Reaction equation

HRID 13262 reaction equation
O.[C:2]1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:13]([O:15][C:16]([C:18]1[CH:19]=[CH:20][C:21]([O:36]COC)=[C:22]([CH:24]2[CH2:28][CH2:27][CH2:26][N:25]2[C:29](OC(C)(C)C)=[O:30])[CH:23]=1)=[O:17])[CH3:14].C(=O)(O)[O-].[Na+].C(OC(=O)C)(=O)C.C(=O)([O-])[O-].[K+].[K+]>C(O)C.O.C(OCC)(=O)C.CO.C(N(CC)CC)C.N1C=CC=CC=1>[C:29]([N:25]1[CH2:26][CH2:27][CH2:28][CH:24]1[C:22]1[CH:23]=[C:18]([CH:19]=[CH:20][C:21]=1[OH:36])[C:16]([O:15][CH2:13][CH3:14])=[O:17])(=[O:30])[CH3:2]

Participants

12

Reactant 5

HCID 7918Acetic Anhydride3×HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 23145317t-Butyl 2-(5-ethoxycarbonyl-2-methoxymethoxy-phenyl)-pyrrolidine-1-carboxylate

Product 1

HCID 23145623Ethyl 3-(1-acetyl-pyrrolidin-2-yl)-4-hydroxybenzoate

Reagents, catalysts & solvents 6

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 1049PyridineSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

13 g of p-toluenesulfonic acid monohydrate was added to a solution of 26 g of t-butyl 2-(5-ethoxycarbonyl-2-methoxymethoxy-phenyl)-pyrrolidine-1-carboxylate in a mixture of 250 ml of ethanol and 50 ml of water, and the reaction liquid was heated under reflux for 2 days. After cooled, the reaction liquid was diluted with water, neutralized with aqueous sodium bicarbonate, extracted with a mixed solvent of chloroform/methanol (10/1), and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure to obtain a crude product. 13 ml of acetic anhydride was added to a pyridine (200 ml) solution of the resulting crude product, and stirred. After 1 hour, 6 ml of acetic anhydride was added to it. Further after 1 hour, 150 ml of pyridine was added to it, and further after 40 minutes, 5 ml of triethylamine was added thereto. Further after 30 minutes, 3 ml of acetic anhydride was added to it, and the reaction liquid was stirred for 30 minutes. The reaction liquid was diluted with ethyl acetate, and washed with aqueous saturated sodium bicarbonate, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried with anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure to obtain a crude product. 10 g of potassium carbonate was added to a methanol (200 ml) solution of the resulting crude product, and the reaction liquid was stirred for 4 hours at room temperature. The reaction liquid was distilled under reduced pressure, and the resulting residue was diluted with aqueous saturated ammonium chloride solution, and extracted with ethyl acetate. This was dried with anhydrous magnesium sulfate, then the solvent was evaporated away under reduced pressure, and the resulting solid was taken out through filtration with ethyl acetate to obtain the entitled compound as a white solid.

Workup

  1. customthe reaction liquid
  2. temperaturewas heated
  3. temperatureunder reflux for 2 days
  4. temperatureAfter cooled
  5. customthe reaction liquid
  6. extractionextracted with a mixed solvent of chloroform/methanol (10/1)
  7. dry with materialdried with anhydrous magnesium sulfate
  8. customThe solvent was evaporated away under reduced pressure
  9. customto obtain a crude product
  10. waitFurther after 1 hour
  11. waitfurther after 40 minutes
  12. waitFurther after 30 minutes
  13. customthe reaction liquid
  14. stirringwas stirred for 30 minutes
  15. customThe reaction liquid
  16. washwashed with aqueous saturated sodium bicarbonate
  17. extractionthe aqueous layer was extracted with ethyl acetate
  18. dry with materialThe combined organic layers were dried with anhydrous magnesium sulfate
  19. customthe solvent was evaporated away under reduced pressure
  20. customto obtain a crude product
  21. customthe reaction liquid
  22. stirringwas stirred for 4 hours at room temperature
  23. customThe reaction liquid
  24. distillationwas distilled under reduced pressure
  25. additionthe resulting residue was diluted with aqueous saturated ammonium chloride solution
  26. extractionextracted with ethyl acetate
  27. dry with materialThis was dried with anhydrous magnesium sulfate
  28. customthe solvent was evaporated away under reduced pressure
  29. filtrationthe resulting solid was taken out through filtration with ethyl acetate

Sources & evidence

ORD record
ord-8c73b84d33c34b4b94f170025f532de0
Source dataset
uspto-grants-2010_06
Patent number
US07728025B2

Reaction notes

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