Trifluoromethanesulfonic anhydride → HCID 66683785, compound

HRID 2370972Notes

Reaction equation

HRID 2370972 reaction equation
[CH:1]1([C:4]2[CH:9]=[C:8]([F:10])[C:7]([N+:11]([O-:13])=[O:12])=[CH:6][C:5]=2[NH:14][C:15](=O)[CH:16]([CH3:18])[CH3:17])[CH2:3][CH2:2]1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C[Si]([N:39]=[N+:40]=[N-:41])(C)C>C(#N)C>[CH:1]1([C:4]2[CH:9]=[C:8]([F:10])[C:7]([N+:11]([O-:13])=[O:12])=[CH:6][C:5]=2[N:14]2[C:15]([CH:16]([CH3:18])[CH3:17])=[N:41][N:40]=[N:39]2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 67749Trifluoromethanesulfonic anhydrideHCID 78378AzidotrimethylsilaneHCID 66684475HCID 66684475, compound

Product 1

HCID 66683785HCID 66683785, compoundYield 81.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
-5 °C

Procedure

N-(2-cyclopropyl-4-fluoro-5-nitrophenyl)isobutyramide (1.90 g, 7.14 mmol, 1 equiv) was dissolved in acetonitrile (40 mL) under argon and cooled to −5° C. (external temperature). While maintaining the temperature at −5° C., trifluoromethanesulfonic anhydride (2.40 mL, 4.03 g, 14.27 mmol, 2 equiv) was added slowly dropwise and stirred for 1-2 minutes. Then trimethylsilyl azide (3.75 mL, 28.54 mmol, 4 equiv) was added slowly dropwise while maintaining the temperature at −5° C. TLC, LCMS indicated the reaction was complete in less than 1 minute. While maintaining the temperature at −5° C., the reaction was slowly quenched with ice-cold saturated NaHCO3 and diluted with EtOAc. The layers were separated, and the organic layer was washed with brine 1×, dried over Na2SO4, and concentrated to dryness. The crude product was absorbed onto silica gel and purified by flash chromatography and eluted with hex:EtOAc=100:0 to 25%-30% EtOAc using 5% EtOAc increments to afford 1-(2-cyclopropyl-4-fluoro-5-nitrophenyl)-5-isopropyl-1H-tetrazole (1.69 g, 78%) as a yellow solid.

Workup

  1. temperatureWhile maintaining the temperature at −5° C.
  2. temperaturewhile maintaining the temperature at −5° C
  3. waitwas complete in less than 1 minute
  4. temperatureWhile maintaining the temperature at −5° C.
  5. customthe reaction was slowly quenched with ice-cold saturated NaHCO3
  6. additiondiluted with EtOAc
  7. customThe layers were separated
  8. washthe organic layer was washed with brine 1×
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated to dryness
  11. customThe crude product was absorbed onto silica gel
  12. custompurified by flash chromatography
  13. washeluted with hex

Sources & evidence

ORD record
ord-baad8162d5644b6ea707e1d2636882bd
Source dataset
uspto-grants-2014_04
Patent number
US08710223B2

Reaction notes

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