Potassium Carbonate → HCID 66613778, compound

HRID 2276016Notes

Reaction equation

HRID 2276016 reaction equation
Br[C:2]1[N:6]([CH3:7])[N:5]=[C:4]([CH3:8])[C:3]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[Cl:17].[F:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.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>[Cl:17][C:11]1[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]=1[O:9][C:3]1[C:4]([CH3:8])=[N:5][N:6]([CH3:7])[C:2]=1[C:22]1[CH:21]=[CH:20][C:19]([F:18])=[CH:24][C:23]=1[F:25]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 66614114HCID 66614114, compound2×

Product 1

HCID 66613778HCID 66613778, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-bromo-4-(2-chloro-4-fluorophenoxy)-1,3-dimethyl-1H-pyrazole (i.e. the product of Step C) (250 mg, 0.78 mmol) in 1,2-dimethoxyethane/water (5 mL, 2:1) was sparged with a subsurface stream of argon for 30 minutes, and then 2,4-difluorophenylboronic acid (371 mg, 2.34 mmol), potassium carbonate (1.08g, 7.82 mmol) and tetrakis(triphenylphosphine)palladium (90 mg, 0.078 mmol) were added. The reaction mixture was heated to 80° C. for 15 h, and then cooled and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel column chromatography (5 to 30% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a pale yellow solid (150 mg) melting at 70-72° C.

Workup

  1. customwas sparged with a subsurface stream of argon for 30 minutes
  2. temperaturecooled
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with water and saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting material was purified by silica gel column chromatography (5 to 30% gradient of ethyl acetate in hexanes as eluant)

Sources & evidence

ORD record
ord-1cd7092790f64fdbac4522899f4c2c8a
Source dataset
uspto-grants-2015_09
Patent number
US09131693B2

Reaction notes

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