Cesium carbonate → 4-Methoxy-2-(2H-1,2,3-triazol-2-yl)benzoic acid

HRID 2175024Notes

Reaction equation

HRID 2175024 reaction equation
Br[C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C([O-])([O-])=O.[Cs+].[Cs+].[N:19]1[NH:20][N:21]=[CH:22][CH:23]=1.CN[C@@H]1CCCC[C@H]1NC>[Cu]I.CCOC(C)=O.O.O1CCOCC1>[CH3:12][O:11][C:9]1[CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]([N:20]2[N:21]=[CH:22][CH:23]=[N:19]2)[CH:10]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 675161H-1,2,3-TriazoleHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 144847132-Bromo-4-methoxybenzoic acid

Product 1

HCID 670869234-Methoxy-2-(2H-1,2,3-triazol-2-yl)benzoic acidYield 68.6%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To 2-bromo-4-methoxybenzoic acid (4 g, 17.3 mmol), CuI (266 mg, 1.4 mmol) and Cs2CO3 (11.2 g, 34.6 mmol) was added dioxane (36 mL), water (94 μL, 5.1 mmol), 2H-1,2,3-triazole (2.0 mL, 34.6 mmol) and (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (683 μL, 4.3 mmol). The reaction mixture was heated to 100° C. for 3 hr. The reaction mixture was cooled rt, then EtOAc and water were added. The mixture was transferred to a separatory funnel and the aqueous layer separated. The aqueous layer was acidified with conc. HCl to pH˜2 and extracted with EtOAc (2×). The organic layers were washed with brine and dried (Na2SO4) to give a yellow solid. This material was slurried with EtOAc (˜20 mL) and the solids filtered (>95% 4-methoxy-2-(1H-1,2,3-triazol-1-yl)benzoic acid by HPLC). Purification (FCC) (50% DCM to 100% DCM containing 10% (5% formic acid/MeOH)) gave the title compound (2.6 g) as a yellow solid. 1H NMR (CDCl3): 7.99-7.90 (m, 1H), 7.83 (s, 2H), 7.20 (d, J=2.5 Hz, 1H), 7.03 (dd, J=8.8, 2.6 Hz, 1H), 3.89 (s, J=17.6 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was cooled rt
  2. customThe mixture was transferred to a separatory funnel
  3. customthe aqueous layer separated
  4. extractionextracted with EtOAc (2×)
  5. washThe organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. customto give a yellow solid
  8. filtrationthe solids filtered (>95% 4-methoxy-2-(1H-1,2,3-triazol-1-yl)benzoic acid by HPLC)
  9. customPurification (FCC) (50% DCM to 100% DCM containing 10% (5% formic acid/MeOH))

Sources & evidence

ORD record
ord-2583afe3c24c4bdb805547a545962662
Source dataset
uspto-grants-2015_06
Patent number
US09062044B2

Reaction notes

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