Boron tribromide → 4-(3-p-Tolyl-[1,2,4]triazol-1-yl)-phenol

HRID 1470805Notes

Reaction equation

HRID 1470805 reaction equation
C1(C)C=CC(C2N=CNN=2)=CC=1.IC1C=CC(OC)=CC=1.B(Br)(Br)Br.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH:38]=[N:37][C:36]([C:39]3[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=3)=[N:35]2)=[CH:30][CH:29]=1>C(Cl)Cl>[CH3:26][O:27][C:28]1[CH:29]=[CH:30][C:31]([N:34]2[CH:38]=[N:37][C:36]([C:39]3[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=3)=[N:35]2)=[CH:32][CH:33]=1.[C:42]1([CH3:45])[CH:41]=[CH:40][C:39]([C:36]2[N:37]=[CH:38][N:34]([C:31]3[CH:32]=[CH:33][C:28]([OH:27])=[CH:29][CH:30]=3)[N:35]=2)=[CH:44][CH:43]=1

Participants

7

Reactant 4

HCID 25134Boron tribromideHCID 696764-IodoanisoleHCID 675191801-(4-Methoxyphenyl)-3-p-tolyl-1H-[1,2,4]triazoleHCID 178423994HCID 178423994, compound

Product 2

HCID 675191801-(4-Methoxyphenyl)-3-p-tolyl-1H-[1,2,4]triazoleHCID 675195054-(3-p-Tolyl-[1,2,4]triazol-1-yl)-phenolYield 136.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-(4-Methoxyphenyl)-3-p-tolyl-1H-[1,2,4]triazole was prepared by coupling 3-p-tolyl-1H-[1,2,4]triazole with 4-iodoanisole under conditions described in Step 1 of the previous example. This material was then demethylated using conditions described in Hitchcock et al. Synlett 2006, 2625. Boron tribromide (1 M solution in hexanes; 1.67 mL, 1.67 mmol) was added dropwise to a solution of 1-(4-methoxyphenyl)-3-p-tolyl-1H-[1,2,4]triazole (300 mg, 1.28 mmol) in DCM (10 mL) at 0° C. under N2. After addition was complete, the vessel was warmed to ambient temperature before refluxing at 40° C. for 6 h. The cooled contents were then quenched with H2O before removal of the DCM and partitioning between EtOAc and water. The organic layer was collected, washed with brine, dried (MgSO4), concentrated, and purified via chromatography (3:1:1, hexanes:EtOAc:acetone) to afford the 4-(3-p-tolyl-[1,2,4]-triazol-1-yl)-phenol intermediate (219 mg, 0.872 mmol, 68%). Trifluoromethanesulfonic anhydride (0.16 mL, 0.96 mmol) was added dropwise to a solution of the phenol and 4-tert-butyl-2,6-dimethylpyridine (142 mg, 0.872 mmol) in DCM (10 mL) at 0° C. under N2. The vessel was warmed to ambient temperature before the solvent was removed under reduced pressure and the residue purified via chromatography (2:2:1, hexanes:EtOAc:acetone) affording the trifluoromethanesulfonic acid 4-(3-p-tolyl-[1,2,4]-triazol-1-yl)-phenyl ester intermediate (304 mg, 0.794 mmol, 91%).

Workup

  1. additionAfter addition
  2. temperaturebefore refluxing at 40° C. for 6 h
  3. customThe cooled contents were then quenched with H2O before removal of the DCM
  4. custompartitioning between EtOAc and water
  5. customThe organic layer was collected
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. custompurified via chromatography (3:1:1, hexanes:EtOAc:acetone)

Sources & evidence

ORD record
ord-120db0a7560a4081bb6d14009a115a17
Source dataset
uspto-grants-2015_04
Patent number
US09006468B2

Reaction notes

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