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

HRID 1259268Notes

Reaction equation

HRID 1259268 reaction equation
I[C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[NH:12]1[CH:16]=[CH:15][N:14]=[N:13]1.CN[C@@H]1CCCC[C@H]1NC>CN(C=O)C.O.[Cu]I>[N:12]1[N:13]([C:2]2[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=2[C:4]([OH:6])=[O:5])[N:14]=[CH:15][CH:16]=1

Participants

7

Reactant 3

HCID 1429412-Iodo-5-methylbenzoic acidHCID 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 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 2-iodo-5-methylbenzoic acid (4.0 g, 15.3 mmol) in DMF (10 mL) was treated with 1,2,3-triazole (2.1 g, 30.5 mmol), CsCO3 (9.95 g, 30.5 mmol), CuI (0.145 g, 0.76 mmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (0.43 g, 3.05 mmol). The mixture was heated at 120° C. for 10 min in a microwave reactor. The reaction was cooled to room temperature, diluted with water, and washed with EtOAc. The aqueous phase was acidified with 1N HCl and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by gradient elution on SiO2 (0 to 10% MeOH in DCM with 0.1% AcOH) to give the faster eluting 2-(2H-1,2,3-triazol-2-yl)-5-methylbenzoic acid A-6, followed by the undesired regioisomer isomer, 1-(2H-1,2,3-triazol-2-yl)-5-methylbenzoic acid. Data for A-6: 1HNMR (500 MHz, DMSO-d6) δ 12.98 (br s, 1H), 8.04 (s, 2H), 7.72-7.45 (m, 3H), 2.41 (s, 3H) ppm.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. washwashed with EtOAc
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by gradient elution on SiO2 (0 to 10% MeOH in DCM with 0.1% AcOH)
  8. customto give the
  9. washfaster eluting 2-(2H-1,2,3-triazol-2-yl)-5-methylbenzoic acid A-6

Sources & evidence

ORD record
ord-c87acb2aeb294a86977db70271448b4c
Source dataset
uspto-grants-2013_06
Patent number
US08466281B2

Reaction notes

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