Citric Acid → HCID 20741412, compound

HRID 1883965Notes

Reaction equation

HRID 1883965 reaction equation
[CH3:1][S:2](Cl)(=O)=O.NC1[C:16](F)=[C:15]([N:18]2[CH2:22][CH2:21][C@@H:20]([CH:23]([NH2:29])[C:24]3OC=CC=3)[CH2:19]2)[C:14](F)=[C:13]2[C:8]=1[C:9](=O)[C:10]([C:35](O)=O)=CN2[C@@H]1C[C@@H]1F.C(O)(=O)CC(CC(O)=O)(C(O)=O)[OH:42].[N-]=[N+:53]=[N-:54].[Na+].C([N:58]([CH2:61]C)CC)C>O.ClCCl>[N:29]([CH:23]([C@H:20]1[CH2:19][N:18]([C@@H:15]([C:14]2[CH:13]=[CH:8][CH:9]=[CH:10][CH:35]=2)[CH3:16])[C:22](=[O:42])[CH2:21]1)[C:24]1[S:2][CH:1]=[CH:61][N:58]=1)=[N+:53]=[N-:54]

Participants

8

Reactant 5

HCID 311Citric AcidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 20741428HCID 20741428, compound

Product 1

HCID 20741412HCID 20741412, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

Under ice-cooling, triethylamine (725 μl) and methanesulfonyl chloride (341 μl, 4.40 mmol) were added to a dichloromethane (20 ml) solution of 4-(R)-[1-hydroxy-1-(thiazol-2-yl)methyl]-1-[1-(R)-phenylethyl]-2-pyrrolidone [F1] (1.21 g, 4.00 mmol), and the mixture was stirred at the same temperature for 1 hour. The reaction solution was mixed with 10% citric acid (30 ml) under ice-cooling and extracted with chloroform (30 ml×2), and the organic layer was washed with saturated brine (100 ml) and then dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure, and the resulting residue was dissolved in N,N-dimethylformamide (30 ml), mixed with sodium azide (780 mg, 12.0 mmol) and then heated at 60° C. for 15 hours. After spontaneous cooling, the reaction solution was mixed with water (70 ml) and extracted with ethyl acetate (80 ml×3), and the organic layer was washed with saturated brine (200 ml) and then dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure, and the resulting residue was applied to a silica gel column chromatography. By eluting with a n-hexane:ethyl acetate system of from (1:2) to (1:3), 1.263 g (96%) of the title compound was obtained as a light yellow oil.

Workup

  1. temperatureUnder ice-cooling
  2. temperaturecooling
  3. extractionextracted with chloroform (30 ml×2)
  4. washthe organic layer was washed with saturated brine (100 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under a reduced pressure
  7. dissolutionthe resulting residue was dissolved in N,N-dimethylformamide (30 ml)
  8. extractionextracted with ethyl acetate (80 ml×3)
  9. washthe organic layer was washed with saturated brine (200 ml)
  10. dry with materialdried over anhydrous sodium sulfate
  11. customThe solvent was evaporated under a reduced pressure
  12. washBy eluting with a n-hexane

Sources & evidence

ORD record
ord-6c1a63729329495db1e040d14227fc5a
Source dataset
uspto-grants-2004_07
Patent number
US06762181B1

Reaction notes

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