Potassium Phosphate, Tribasic → HCID 89649591, compound

HRID 2207628Notes

Reaction equation

HRID 2207628 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.[CH3:17][C:18]1[CH:22]=[CH:21][NH:20][N:19]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N[C@H]1CCCC[C@@H]1N>O1CCOCC1.O.CCOC(C)=O.[Cu]I>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([N:20]2[CH:21]=[CH:22][C:18]([CH3:17])=[N:19]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 62657Potassium Phosphate, TribasicHCID 4793071,2-Diaminocyclohexane, (+)-HCID 73553470HCID 73553470, compoundHCID 178428694HCID 178428694, compound

Product 1

HCID 89649591HCID 89649591, compoundYield 23%

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 3-methyl-1H-pyrazole (525.68 mg, 6.4 mmol) in 1,4-dioxane (10 mL) was added copper (I) iodide (101.62 mg, 0.5300 mmol), potassium phosphate (2265.26 mg, 10.67 mmol), and (1S,2S)-(+)-1,2-diaminocyclohexane (60.93 mg, 0.5300 mmol). The vial was sealed and heated in a microwave at 200° C. for 2 h 30 minutes. The reaction 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 (50 g, SNAP cartidge), eluting with a gradient of EtOAc:isohexane from 0% to 30%. Fractions containing the first eluting product were combined and concentrated in vacuo to give 1-(3-benzyloxy-4-fluoro-phenyl)-3-methyl-pyrazole (D66) (385 mg, 1.2274 mmol, 23% yield) as a colourless oil which crystallised on standing;

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 (50 g, SNAP cartidge)
  8. washeluting with a gradient of EtOAc
  9. additionFractions containing the first eluting product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3b52a3c157eb45eb859f1eb531b11ab4
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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