Oxalyl chloride → HCID 58468226, compound

HRID 1807486Notes

Reaction equation

HRID 1807486 reaction equation
I[C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH:12]1[CH:16]=[CH:15][N:14]=[N:13]1.CN[C@@H]1CCCC[C@H]1NC.C(Cl)(=O)C([Cl:30])=O>CN(C=O)C.O.C(Cl)Cl.[Cu]I>[CH3:11][C:8]1[CH:9]=[CH:10][C:2]([N:13]2[N:14]=[CH:15][CH:16]=[N:12]2)=[C:3]([CH:7]=1)[C:4]([Cl:30])=[O:6]

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 1429412-Iodo-5-methylbenzoic acidHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 178418936HCID 178418936, compound

Product 1

HCID 58468226HCID 58468226, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

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-2, followed by the undesired regioisomer isomer, 1-(2H-1,2,3-triazol-2-yl)-5-methylbenzoic acid. A solution of the acid (3.56 g, 17.52 mmol) in 150 mL of DCM was stirred and cooled to 0° C. The solution was treated with oxalyl chloride (1.9 mL, 21.9 mmol) and DMF (68 μL, 0.878 mmol). The solution was slowly warmed to room temperature and stirred overnight. Solvent was concentrated and the resulting solid was azetroped with DCM and concentrated to provide A-4 as a yellow solid.

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-2
  10. temperaturecooled to 0° C
  11. temperatureThe solution was slowly warmed to room temperature
  12. concentrationSolvent was concentrated
  13. concentrationconcentrated
  14. customto provide A-4 as a yellow solid

Sources & evidence

ORD record
ord-febe13c2fb1043e5944bd8c5dbb813d9
Source dataset
uspto-grants-2013_01
Patent number
US08357700B2

Reaction notes

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