Sodium Iodide → HCID 57907463, compound

HRID 243686Notes

Reaction equation

HRID 243686 reaction equation
[CH2:1]([O:8][C:9](=[O:26])[CH:10](Br)[CH2:11][CH2:12][C:13]1[CH:17]=[CH:16][N:15](C(OC(C)(C)C)=O)[N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>ClCCl>[N:15]1[N:14]2[CH:10]([C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:26])[CH2:11][CH2:12][C:13]2=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 57907576HCID 57907576, compound

Product 1

HCID 57907463HCID 57907463, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 16.9 g (40.0 mmol) of tert-butyl 3-[4-(benzyloxy)-3-bromo-4-oxobutyl]-1H-pyrazole-1-carboxylate from step E above in 50 mL of dichloromethane was added 50 mL of TFA. The resulting mixture was stirred for 2 h at ambient temperature then all volatiles were evaporated in vacuo. The residue was then diluted with 50 mL of toluene and evaporated again in vacuo to remove all residual TFA. The crude material was then dissolved in 125 mL of anhydrous acetone and 14.0 g (100 mmol) of solid potassium carbonate was slowly added over 15 min followed by 1.2 g (8.0 mmol) of sodium iodide. The resulting mixture was then heated at reflux for 16 h, cooled to room temperature and evaporated to dryness in vacuo. The residue was diluted with 100 mL of a saturated, aqueous ammonium chloride solution and then extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated in vacuo. The crude residue was purified by silica gel chromatography eluting with a 10-80% ethyl acetate in hexanes gradient to afford the title compound as a clear gum 6.2 g (64% yield). LC-MS: m/z (ES) 243 (MH)+.

Workup

  1. customall volatiles were evaporated in vacuo
  2. additionThe residue was then diluted with 50 mL of toluene
  3. customevaporated again in vacuo
  4. customto remove all residual TFA
  5. dissolutionThe crude material was then dissolved in 125 mL of anhydrous acetone
  6. temperatureThe resulting mixture was then heated
  7. temperatureat reflux for 16 h
  8. temperaturecooled to room temperature
  9. customevaporated to dryness in vacuo
  10. additionThe residue was diluted with 100 mL of a saturated, aqueous ammonium chloride solution
  11. extractionextracted with ethyl acetate (3×100 mL)
  12. washThe combined organic layers were washed with brine
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. customevaporated in vacuo
  16. customThe crude residue was purified by silica gel chromatography
  17. washeluting with a 10-80% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-358055f4eab74151ab06069a092b14a6
Source dataset
uspto-grants-2014_02
Patent number
US08653260B2

Reaction notes

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