Tetrabutylammonium Hydroxide → 3-(Tetrazol-1-yl)cyanopyridine

HRID 857725Notes

Reaction equation

HRID 857725 reaction equation
[NH:1]1[CH:5]=[N:4][N:3]=[N:2]1.[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.F[C:25]1[C:26]([C:31]#[N:32])=[N:27][CH:28]=[CH:29][CH:30]=1>CN(C=O)C>[N:1]1([C:25]2[C:26]([C:31]#[N:32])=[N:27][CH:28]=[CH:29][CH:30]=2)[CH:5]=[N:4][N:3]=[N:2]1

Participants

5

Reactant 3

HCID 2723671Tetrabutylammonium HydroxideHCID 70604082-Cyano-3-fluoropyridine2×HCID 178418441HCID 178418441, compound

Product 1

HCID 218662973-(Tetrazol-1-yl)cyanopyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of tetrazole (1.0 g; 14 mmol) in DMF (150 mL) was added 40% aqueous tetrabutylammonium hydroxide (7.8 g; 12 mmol). The solvent was removed under reduced pressure. To ensure removal of all the water from the tetrabutylammonium hydroxide solution, the residue was redissolved in DMF and the solution was evaporated under reduced pressure. This procedure was repeated a total of three times. The residue was then dissolved in DMF (60 mL) and 3-fluoro-2-cyanopyridine (1.5 g; 12 mmol) was added. The reaction was stirred at ambient temperature under inert atmosphere for four days, at which time hplc analysis indicated about 65% conversion of the 3-fluoro-2-cyanopyridine to new products. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc and water. The EtOAc layer was separated, dried over anhydrous MgSO4, and filtered. The solvent was removed under reduced pressure and the residue was purified by flash chromatography using a gradient elution of 1:4 to 100:0 EtOAc:hexanes to give 3-(tetrazol-1-yl)cyanopyridine as a white crystalline solid (TLC Rf=0.5, 1:1 EtOAc-hexanes; hplc retention time=2.04 min, method X; 1H NMR (CDCl3) δ 9.42 (s, 1H), 8.94 (dd, J=1.3, 4.6 Hz, 1H), 8.31 (dd, J=1.3, 8.4 Hz, 1H), 7.87 (dd, J=4.6, 8.4 Hz, 1H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customremoval of all the water from the tetrabutylammonium hydroxide solution
  3. dissolutionthe residue was redissolved in DMF
  4. customthe solution was evaporated under reduced pressure
  5. dissolutionThe residue was then dissolved in DMF (60 mL)
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was partitioned between EtOAc and water
  8. customThe EtOAc layer was separated
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. customThe solvent was removed under reduced pressure
  12. customthe residue was purified by flash chromatography
  13. washa gradient elution of 1:4 to 100:0 EtOAc

Sources & evidence

ORD record
ord-bbc7c487afdf44649fdd9311db992535
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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