Pyrazole → HCID 89648808, compound

HRID 2207631Notes

Reaction equation

HRID 2207631 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13](Br)[CH:12]=[CH:11][C:10]=1[F:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N[C@H]1CCCC[C@@H]1N.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[NH:33]1[CH:37]=[CH:36][CH:35]=[N:34]1>O1CCOCC1.O.CCOC(C)=O.[Cu]I>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([N:33]2[CH:37]=[CH:36][CH:35]=[N:34]2)[CH:12]=[CH:11][C:10]=1[F:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 1048PyrazoleHCID 62657Potassium Phosphate, TribasicHCID 4793071,2-Diaminocyclohexane, (+)-HCID 73553470HCID 73553470, compound

Product 1

HCID 89648808HCID 89648808, compoundYield 43.1%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
200 °C

Procedure

To a microwave vial containing 2-benzyloxy-4-bromo-1-fluoro-benzene [CAS: 1036724-54-5] (1500 mg, 5.34 mmol) and (1S,2S)-(+)-1,2-diaminocyclohexane (121.86 mg, 1.07 mmol) in 1,4-dioxane (10 mL) was added copper (I) iodide (203.24 mg, 1.07 mmol), potassium phosphate (2265.3 mg, 10.67 mmol), and 1H-pyrazole (363.26 mg, 5.34 mmol). The vial was sealed and heated in a microwave at 200° C. for 1 hour. The reaction mixture was diluted with water (50 mL) and EtOAc (30 mL), and the organics were separated, washed with brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography over silica (25 g, SNAP cartridge), eluting with a gradient of EtOAc:isohexane from 0% to 30%. Fractions containing desired product were combined and concentrated in vacuo to give 1-(3-benzyloxy-4-fluoro-phenyl)pyrazole (D71) (649.1 mg, 2.2984 mmol, 43.1% yield) as a pale orange oil;

Workup

  1. customThe vial was sealed
  2. customthe organics were separated
  3. washwashed with brine (20 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography over silica (25 g, SNAP cartridge)
  8. washeluting with a gradient of EtOAc
  9. additionFractions containing desired product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e99c7d7f2bae45f5a4008bba8bde969b
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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