Water → HCID 66652937, compound

HRID 2283640

Reaction equation

HRID 2283640 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1B(O)O.Br[C:17]1[C:18]([N+:28]([O-:30])=[O:29])=[N:19][N:20]([CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[CH:21]=1.BrC1C=NN(C2CCCCO2)C=1[N+]([O-])=O.O>COCCOC.C(=O)([O-])[O-].[K+].[K+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N+:28]([C:18]1[C:17]([C:3]2[CH:4]=[C:5]([O:8][C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:7][C:2]=2[OH:1])=[CH:21][N:20]([CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[N:19]=1)([O-:30])=[O:29]

Participants

8

Reactant 4

HCID 962WaterHCID 666527944-bromo-3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazoleHCID 666531524-bromo-5-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazoleHCID 66655615HCID 66655615, compound

Product 1

HCID 66652937HCID 66652937, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-hydroxy-5-(trifluoromethoxy)phenylboronic acid (Preparation 23, 20.5 g, 92.4 mmol) and 4-bromo-3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole or 4-bromo-5-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (Preparation 22, 22.7 g, 82.2 mmol) in 1,2-dimethoxyethane (300 mL) and 2 M potassium carbonate in water (117 mL, 212 mmol) was added tetrakis(triphenylphosphine)palladium(0) (5.0 g, 4.3 mmol). The solution was sparged with argon (×3) and heated at 80° C. for 8 hours. The reaction mixture was cooled to ambient temperature and the layers separated. The aqueous phase was washed with ethyl acetate (×2). The combined organic phase was dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (0 to 30% ethyl acetate in hexanes gradient elution) and concentrated in vacuo. Excess hexanes was added to the residue and the resulting solid was collected by filtration and dried in vacuo to afford the title compound as off white crystals (19.5 g).

Workup

  1. customThe solution was sparged with argon (×3)
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. customthe layers separated
  4. washThe aqueous phase was washed with ethyl acetate (×2)
  5. dry with materialThe combined organic phase was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (0 to 30% ethyl acetate in hexanes gradient elution)
  8. concentrationconcentrated in vacuo
  9. additionExcess hexanes was added to the residue
  10. filtrationthe resulting solid was collected by filtration
  11. customdried in vacuo

Sources & evidence

ORD record
ord-1ef9ecefa3de4463937a3de935c4744e
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Linked notes

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