2-Iodobenzoic acid → 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid

HRID 2370253Notes

Reaction equation

HRID 2370253 reaction equation
I[C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[NH:11]1[CH:15]=[CH:14][N:13]=[N:12]1.[C:16]([O-])([O-])=O.[Cs+].[Cs+].CN[C@@H]1CCCC[C@H]1NC>CN(C=O)C.CCOC(C)=O.[Cu]I>[CH3:16][C:8]1[CH:9]=[CH:10][C:2]([N:12]2[N:13]=[CH:14][CH:15]=[N:11]2)=[C:3]([CH:7]=1)[C:4]([OH:6])=[O:5]

Participants

8

Reactant 4

HCID 69412-Iodobenzoic acidHCID 10796Cesium carbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 178418936HCID 178418936, compound

Product 1

HCID 532601655-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 2-iodobenzoic acid (3.0 g, 12.09 mmol) in DMF was treated with 1,2,3-triazole (1.5 g, 21.7 mmol), Cs2CO3 (7.08 g, 21.7 mmol), CuI (114 mg, 0.60 mmol), and trans-N,N′-dimethylcyclohexane-1,2-diamine (310 mg, 2.17 mmol). The mixture was heated at 120° C. for 10 min in a microwave reactor. The reaction was cooled to room temperature, diluted with EtOAc, and filtered through Celite®. The residue was purified by gradient elution on SiO2 (0 to 10% MeOH/DCM with 0.1% AcOH) to provide the faster eluting title compound as a white solid. Data for D-1: 1H NMR (500 MHz, DMSO-d6) δ 13.05 (br s, 1H), 8.12 (s, 2H), 7.81-7.52 (m, 4H). The undesired 1-(2H-1,2,3-triazol-2-yl)benzoic acid (D-2) eluted second. 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid (D-3) was prepared in an analogous manner.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltered through Celite®
  3. customThe residue was purified by gradient elution on SiO2 (0 to 10% MeOH/DCM with 0.1% AcOH)
  4. customto provide the
  5. washfaster eluting title compound as a white solid
  6. washThe undesired 1-(2H-1,2,3-triazol-2-yl)benzoic acid (D-2) eluted second

Sources & evidence

ORD record
ord-13b2cb4a598642e9b8bbc62ced592ab9
Source dataset
uspto-grants-2014_04
Patent number
US08710076B2

Reaction notes

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