Pyridine → HCID 89710890, compound

HRID 1477252Notes

Reaction equation

HRID 1477252 reaction equation
[CH3:1][CH:2](O)[CH3:3].N1C=CC=CC=1.[F:11][C:12]([F:25])([F:24])[S:13]([O:16]S(C(F)(F)F)(=O)=O)(=[O:15])=[O:14].[CH3:26][C:27]1[CH:32]=[C:31]([CH3:33])[CH:30]=[C:29]([CH3:34])[C:28]=1[N:35]1[CH:39]=[C:38]([C:40]2[C:45]([CH3:46])=[CH:44][C:43]([CH3:47])=[CH:42][C:41]=2[CH3:48])[N:37]=[N:36]1>ClCCl.CCCCC>[NH+:35]1[NH:36][N:37]=[CH:38][CH:39]=1.[F:11][C:12]([F:25])([F:24])[S:13]([O-:16])(=[O:15])=[O:14].[CH3:26][C:27]1[CH:32]=[C:31]([CH3:33])[CH:30]=[C:29]([CH3:34])[C:28]=1[NH+:35]1[CH:39]=[C:38]([C:40]2[C:45]([CH3:46])=[CH:44][C:43]([CH3:47])=[CH:42][C:41]=2[CH3:48])[N:37]([CH:2]([CH3:3])[CH3:1])[NH:36]1

Participants

8

Reactant 4

HCID 1049PyridineHCID 3776IsopropanolHCID 67749Trifluoromethanesulfonic anhydrideHCID 67468310HCID 67468310, compound

Product 2

HCID 571967762H-triazol-1-iumHCID 89710890HCID 89710890, compoundYield 120.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8003PentaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 2-propanol (690 μL, 9.0 mmol) and pyridine (750 μL, 9.3 mmol) in dichloromethane (5 mL) at −78° C. is added trifluoromethanesulfonic anhydride (1.5 mL, 8.9 mmol). The resulting mixture is stirred at −78° C. for 30 min, and then stirred an additional 30 min as is allowed to slowly reach room temperature. Pentane (10 mL) is added to precipitate the pyridinium salt byproduct, and contents are transferred via filter cannula into a solution of 1,4-bis(2,4,6-trimethylphenyl)-1H-1,2,3-triazole (915 mg, 3 mmol) in dichloromethane (5 mL) at 78° C. The resulting mixture is stirred at −78° C. for 30 min, and then stirred an additional 30 min as is allowed to slowly reach room temperature. Solvents are then evaporated under reduced pressured until a total volume of ca. 5 mL is reached, and additional dichloromethane (5 mL) is added. The mixture is stirred at room temperature overnight, followed by an additional 3 hour at 50° C. Evaporation of the volatiles under reduced pressure affords a crude product that is purified by column chromatography on SiO2 using 98:2 to 90:10 dichloromethane:methanol (v/v) as the mobile phase, and then by reprecipitation from dichloromethane into an excess of diethyl ether to afford triazolium salt 1d as a white solid (902 mg, 60%). 1H-NMR (CD3CN, 300 MHz): δ=8.65 (s, 1H), 7.23 (s, 2H), 7.20 (s, 2H), 4.67 (sept, J=6.8 Hz, 1H), 2.41 (s, 3H), 2.40 (s, 3H), 2.14 (s, 6H), 2.13 (s, 6H), 1.61 (d, J=6.8 Hz, 6H). 13C-NMR (CDCl3, 75 MHz): δ=144.1, 143.7, 142.2, 139.5, 135.6, 133.2, 132.7, 131.6, 130.9, 130.2, 57.5, 22.7, 21.5, 21.4, 20.5, 17.5. HR-MS (ESI): Calcd. for C23H30N3 [M+]: 348.2434. found 348.2436. M.p.: 180-181° C.

Workup

  1. stirringstirred an additional 30 min
  2. customas is allowed to slowly reach room temperature
  3. customto precipitate the pyridinium salt byproduct, and contents
  4. stirringThe resulting mixture is stirred at −78° C. for 30 min
  5. stirringstirred an additional 30 min
  6. customas is allowed to slowly reach room temperature
  7. customSolvents are then evaporated
  8. additionadditional dichloromethane (5 mL) is added
  9. stirringThe mixture is stirred at room temperature overnight
  10. waitfollowed by an additional 3 hour at 50° C
  11. customEvaporation of the volatiles under reduced pressure
  12. customaffords a crude product that
  13. customis purified by column chromatography on SiO2 using 98:2 to 90:10 dichloromethane
  14. custommethanol (v/v) as the mobile phase, and then by reprecipitation from dichloromethane into an excess of diethyl ether

Sources & evidence

ORD record
ord-8c12539a0e1844a7877d1c0096735677
Source dataset
uspto-grants-2016_08
Patent number
US09403781B2

Reaction notes

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