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

HRID 708954Notes

Reaction equation

HRID 708954 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 (1M 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 CH2Cl2 (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 CH2Cl2 and partitioning between EtOAc and H2O. 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 CH2Cl2 (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 CH2Cl2
  4. custompartitioning between EtOAc and H2O
  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-a6f632419a6d41c8a9a1613a0e57a966
Source dataset
uspto-grants-2015_11
Patent number
US09179681B2

Reaction notes

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