Sodium Hydroxide → (3R,4S)-1-((Benzyloxy)carbonyl)-4-hydroxypyrrolidine-3-carboxylic acid

HRID 1446142Notes

Reaction equation

HRID 1446142 reaction equation
[OH:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:4][C@H:3]1[C:17]([O:19]CC)=[O:18].[OH-].[Na+]>C(O)C.O>[CH2:10]([O:9][C:7]([N:5]1[CH2:6][C@@H:2]([OH:1])[C@H:3]([C:17]([OH:19])=[O:18])[CH2:4]1)=[O:8])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 591710451-benzyl 3-ethyl (3R,4S)-4-hydroxypyrrolidine-1,3-dicarboxylate

Product 1

HCID 25418029(3R,4S)-1-((Benzyloxy)carbonyl)-4-hydroxypyrrolidine-3-carboxylic acidYield 87.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

42.1 g of 1-benzyl 3-ethyl (3R,4S)-4-hydroxypyrrolidine-1,3-dicarboxylate (equivalent to 114 mmol) was suspended in 330 mL of ethanol. To this suspension, 330 mL of water was added and the mixture was cooled in an ice bath. While the mixture was stirred, 6.84 g of a solution of sodium hydroxide (171 mmol) in 330 mL of water was added dropwise at an internal temperature of 5 to 10° C. and the mixture was stirred for 1 hour. Subsequently, 6.60 g of activated carbon was added and the mixture was stirred at room temperature for 30 minutes. The insoluble material was separated by filtration through Celite and washed with 110 mL of water. The filtrate and the wash were combined and ethanol (approx. 330 mL) was evaporated under reduced pressure. The resulting residue was washed twice with 200 mL of diisopropyl ether and the aqueous layer was filtered through Celite. 30.0 mL of 6 mol/L hydrochloric acid was added to the filtrate and the mixture was stirred for 10 minutes. 300 mL of ethyl acetate and 200 g of sodium chloride were added and the mixture was further stirred for 30 minutes. The organic layer was collected and washed with 300 mL of 28% brine. To this layer, 30.1 g of anhydrous sodium sulfate was added and the mixture was stirred for 30 minutes. The mixture was then filtered through a cotton plug and washed with 50 mL of ethyl acetate. The filtrate and the wash were combined and concentrated under reduced pressure. The resulting residue was dried in vacuo at room temperature for 4 hours to give 26.5 g of a crude product of the title compound as a dark brown amorphous material. This product was used in the subsequent step without further purification.

Workup

  1. temperaturethe mixture was cooled in an ice bath
  2. stirringthe mixture was stirred for 1 hour
  3. additionSubsequently, 6.60 g of activated carbon was added
  4. stirringthe mixture was stirred at room temperature for 30 minutes
  5. customThe insoluble material was separated by filtration through Celite
  6. washwashed with 110 mL of water
  7. customethanol (approx. 330 mL) was evaporated under reduced pressure
  8. washThe resulting residue was washed twice with 200 mL of diisopropyl ether
  9. filtrationthe aqueous layer was filtered through Celite
  10. addition30.0 mL of 6 mol/L hydrochloric acid was added to the filtrate
  11. stirringthe mixture was stirred for 10 minutes
  12. addition300 mL of ethyl acetate and 200 g of sodium chloride were added
  13. stirringthe mixture was further stirred for 30 minutes
  14. customThe organic layer was collected
  15. washwashed with 300 mL of 28% brine
  16. additionTo this layer, 30.1 g of anhydrous sodium sulfate was added
  17. stirringthe mixture was stirred for 30 minutes
  18. filtrationThe mixture was then filtered through a cotton plug
  19. washwashed with 50 mL of ethyl acetate
  20. concentrationconcentrated under reduced pressure
  21. customThe resulting residue was dried in vacuo at room temperature for 4 hours

Sources & evidence

ORD record
ord-e3a3938bbb9d48b1bd214e243555347b
Source dataset
uspto-grants-2010_02
Patent number
US07667049B2

Reaction notes

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