Citric Acid → HCID 20741411, compound

HRID 348397Notes

Reaction equation

HRID 348397 reaction equation
CS(Cl)(=O)=O.O[CH:7]([C@H:14]1[CH2:18][N:17]([C@@H:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH3:20])[C:16](=[O:27])[CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[N-:41]=[N+:42]=[N-:43].[Na+]>O.ClCCl.C(N(CC)CC)C>[N:41]([CH:7]([C@H:14]1[CH2:18][N:17]([C@@H:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH3:20])[C:16](=[O:27])[CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[N+:42]=[N-:43]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 20741415HCID 20741415, compound

Product 1

HCID 20741411HCID 20741411, compoundYield 87.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

Under ice cooling, triethylamine (0.46 ml) and methanesulfonyl chloride (217 μl, 2.80 mmol) were added to a dichloromethane (10 ml) solution of 4-(R)-[1-hydroxy-1-phenylmethyl]-1-[1-(R)-phenylethyl]-2-pyrrolidone [F1] (738 mg, 2.50 mmol), followed by stirring at the same temperature for 1 hour. To the reaction solution was added 10% citric acid (20 ml) under ice cooling, and the mixture was extracted with chloroform (30 ml×2). After washing with saturated saline (100 ml), the organic layer was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in N,N-dimethylformamide (10 ml). Then, sodium azide (488 mg, 7.50 mmol) was added thereto, followed by stirring at 60° C. for 1.5 hours. After cooling on standing, water (50 ml) was added to the reaction solution and the resulting mixture was extracted with ethyl acetate (70 ml×3). The organic layer was washed with saturated saline (150 ml) and dried over anhydrous sodium sulfate. After removal of the solvent under reduced pressure, the residue was subjected to silica gel column chromatography. Elution with n-hexane/ethyl acetate (3/2) afforded the title compound (701 mg, 87%) as a colorless oil.

Workup

  1. extractionthe mixture was extracted with chloroform (30 ml×2)
  2. washAfter washing with saturated saline (100 ml)
  3. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. dissolutionthe residue was dissolved in N,N-dimethylformamide (10 ml)
  6. stirringby stirring at 60° C. for 1.5 hours
  7. temperatureAfter cooling
  8. extractionthe resulting mixture was extracted with ethyl acetate (70 ml×3)
  9. washThe organic layer was washed with saturated saline (150 ml)
  10. dry with materialdried over anhydrous sodium sulfate
  11. customAfter removal of the solvent under reduced pressure
  12. washElution with n-hexane/ethyl acetate (3/2)

Sources & evidence

ORD record
ord-cf6e5fa3043349e2aa8878f114fbbc23
Source dataset
uspto-grants-2007_02
Patent number
US07176313B2

Reaction notes

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