Cesium carbonate → 5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoic acid

HRID 1750467Notes

Reaction equation

HRID 1750467 reaction equation
[N:1]1[NH:2][N:3]=[CH:4][CH:5]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN[C@@H]1CCCC[C@H]1NC.[F:22][C:23]1[CH:24]=[CH:25][C:26](I)=[C:27]([CH:31]=1)[C:28]([OH:30])=[O:29]>CN(C=O)C.[Cu]I.O>[F:22][C:23]1[CH:24]=[CH:25][C:26]([N:2]2[N:3]=[CH:4][CH:5]=[N:1]2)=[C:27]([CH:31]=1)[C:28]([OH:30])=[O:29].[F:22][C:23]1[CH:24]=[CH:25][C:26]([N:1]2[CH:5]=[CH:4][N:3]=[N:2]2)=[C:27]([CH:31]=1)[C:28]([OH:30])=[O:29]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 675161H-1,2,3-TriazoleHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 131585835-Fluoro-2-iodobenzoic acid

Product 2

HCID 670869485-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoic acidHCID 840153305-fluoro-2-(1H-1,2,3-triazol-1-yl)benzoic acid

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

To a solution of 2H-1,2,3-triazole (CAS number 288-36-8; 4.0 g, 57.97 mmol) in DMF (14.0 ml) was added cesium carbonate (18.84 g, 57.97 mmol), trans-1-N,2-N-dimethylcyclohexane-1,2-diamine (0.510 g, 5.797 mmol), copper(I) iodide (0.276 g, 1.449 mmol) and 5-fluoro-2-iodobenzoic acid (CAS number 52548-63-7; 7.71 g, 28.98 mmol) at 0-10° C. The resulting reaction mixture was then heated with microwave irradiation at 125° C. for 15 hours with stirring. The reaction mass was poured into water and the product was extracted into ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. This was then purified by column chromatography (silica, 0-3% methanol/DCM) to obtain 5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoic acid (Intermediate 8) (also commercially available CAS number 1186050-64-5) and crude 5-fluoro-2-(1H-1,2,3-triazol-1-yl)benzoic acid (Intermediate 9).

Workup

  1. customThe resulting reaction mixture
  2. extractionthe product was extracted into ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThis was then purified by column chromatography (silica, 0-3% methanol/DCM)

Sources & evidence

ORD record
ord-e8bb8a4290a0423f94a6c043a7c6a861
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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