Dimethylformamide → Methyl 4-(4-methyl-5-(2-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-3-yl)bicyclo[2.2.2]octane-1-carboxylate

HRID 2079830Notes

Reaction equation

HRID 2079830 reaction equation
[CH3:1][NH:2][C:3]([C:5]12[CH2:12][CH2:11][C:8]([C:13]([O:15][CH3:16])=[O:14])([CH2:9][CH2:10]1)[CH2:7][CH2:6]2)=O.C(Cl)(=O)C(Cl)=O.CN(C=O)C.[F:28][C:29]([F:42])([F:41])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[C:36]1NN=[N:38][N:37]=1>C(Cl)Cl>[CH3:1][N:2]1[C:36]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[C:29]([F:28])([F:42])[F:41])=[N:37][N:38]=[C:3]1[C:5]12[CH2:12][CH2:11][C:8]([C:13]([O:15][CH3:16])=[O:14])([CH2:9][CH2:10]1)[CH2:7][CH2:6]2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 22591692HCID 22591692, compoundHCID 178506136HCID 178506136, compound

Product 1

HCID 20755116Methyl 4-(4-methyl-5-(2-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-3-yl)bicyclo[2.2.2]octane-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Carboxylate 1-B (2.76 g, 12.3 mmol) was dissolved in methylene chloride (100 ml). Oxalyl chloride (2.0 M, 15.3 ml) was added to the resulting solution followed by DMF (0.19 ml, 2.45 mmol). The reaction mixture was then stirred at room temperature under a nitrogen atmosphere for 2 hours before it was concentrated and stripped from toluene 3 times. The residue was redissolved in toluene (100 ml), treated with 5-[2-(trifluoromethyl)phenyl]-1H-tetrazole (3.15 g, 14.7 mmol) and heated at 100° C. under nitrogen for 12 hours. The product, 1,2,4-triazole 1-C, which precipitated out of reaction mixture as the HCl salt, was dissolved in methylene chloride, washed twice with saturated aqueous sodium bicarbonate solution, dried (MgSO4) and stripped to yield 1-C as a white solid. MS (ESI+)=394.2 (M+1); 1H NMR (500 MHz, CDCl3): δ 2.00 (6H, m), 2.18 (6H, m), 3.48 (3H, s), 3.72 (3H, s), 7.51 (1H, m), 7.71 (2H, m), 7.85 (1H, m) ppm.

Workup

  1. concentrationwas concentrated
  2. dissolutionThe residue was redissolved in toluene (100 ml)
  3. temperatureheated at 100° C. under nitrogen for 12 hours
  4. customThe product, 1,2,4-triazole 1-C, which precipitated out of reaction mixture as the HCl salt
  5. dissolutionwas dissolved in methylene chloride
  6. washwashed twice with saturated aqueous sodium bicarbonate solution
  7. dry with materialdried (MgSO4)

Sources & evidence

ORD record
ord-a856bdc3c1ba418ab2d7f156f2b38b0e
Source dataset
uspto-grants-2011_04
Patent number
US07932280B2

Reaction notes

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