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

HRID 869022Notes

Reaction equation

HRID 869022 reaction equation
[F:1][C:2]1[C:3](I)=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].C([O-])([O-])=O.[Cs+].[Cs+].[N:18]1[NH:19][N:20]=[CH:21][CH:22]=1.CN(C)[C@@H]1CCCC[C@H]1N>O1CCOCC1.O.[Cu]I>[F:1][C:2]1[C:3]([N:18]2[CH:22]=[CH:21][N:20]=[N:19]2)=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 675161H-1,2,3-TriazoleHCID 11275066(1R,2R)-N1,N1-Dimethylcyclohexane-1,2-diamineHCID 223203083-Fluoro-2-iodobenzoic acid

Product 1

HCID 670871113-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 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To 3-fluoro-2-iodobenzoic acid (4.5 g, 16.9 mmol) dissolved in dioxane (33.8 mL) and H2O (0.09 mL) was added Cs2CO3 (11.02 g, 33.8 mmol), CuI (161 mg, 0.85 mmol), 2H-1,2,3-triazole (1.96 mL, 33.8 mmol), and trans-N,N-dimethyl-1,2-cyclohexanediamine (0.53 mL, 3.38 mmol). The mixture was then heated to 100° C. overnight, cooled to room temperature, diluted with H2O, and extracted with EtOAc. The aqueous layer was then acidified and extracted with EtOAc. The combined organics were dried and concentrated. From this concentrate a solid precipitated to provide intermediate A-33 (285 mg, 8%). MS (ESI) mass calcd for C9H6FN3O2, 207.0. m/z found 208.1 [M+H]+. 1H NMR (500 MHz, Methanol-d4) δ 6.81-6.77 (m, 1H), 6.46-6.40 (m, 2H), 6.30-6.23 (m, 1H), 6.18-6.12 (m, 1H).

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with EtOAc
  3. extractionextracted with EtOAc
  4. customThe combined organics were dried
  5. concentrationconcentrated
  6. concentrationFrom this concentrate a solid
  7. customprecipitated
  8. customto provide intermediate A-33 (285 mg, 8%)

Sources & evidence

ORD record
ord-9bef943801574c0c9548f24bf3b6d421
Source dataset
uspto-grants-2015_03
Patent number
US08969352B2

Reaction notes

Loading…