Potassium Carbonate → HCID 86718607, compound

HRID 1480641Notes

Reaction equation

HRID 1480641 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH3:14].[F:22][C:23]([F:34])([F:33])[C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][N:25]=1.C(=O)([O-])[O-].[K+].[K+]>C(COC)OC.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>[F:21][C:17]1[CH:16]=[C:15]([C:4]2[CH:5]=[CH:6][C:7]([O:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH3:14])=[C:2]([C:27]3[CH:28]=[CH:29][C:24]([C:23]([F:34])([F:33])[F:22])=[N:25][CH:26]=3)[CH:3]=2)[CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 251342782-(Trifluoromethyl)pyridine-5-boronic AcidHCID 86718605HCID 86718605, compound

Product 1

HCID 86718607HCID 86718607, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-bromo-3′-fluoro-4-((2-methoxyethoxy)methoxy)-1,1′-biphenyl (1.56 g, 4.39 mmol), 2-(trifluoromethyl)pyridine-5-boronic acid [purchased from Frontier Scientific] (1.09 g, 5.709 mmol) and potassium carbonate (0.91 g, 6.59 mmol) in dimethoxyethane (15 mL) and water (5 mL) was purged with nitrogen for 20 minutes. Tetrakis(triphenylphosphine)palladium(0) (253.8 mg, 0.22 mmol) was added and the reaction mixture heated at 80° C. in a sealed vial for 2 days. The cooled reaction mixture was partitioned between ethyl acetate (80 mL) and 1.0 M aqueous sodium hydroxide solution (80 mL), the organic phase separated, washed with water (80 mL) and saturated brine (80 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give a yellow syrup. The crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 20% ethyl acetate (containing 2% methanol) in hexanes to give 5-(3′-fluoro-4-((2-methoxyethoxy)methoxy)-[1,1′-biphenyl]-3-yl)-2-(trifluoromethyl)pyridine (1.62 g, 88% yield) as a yellow syrup.

Workup

  1. customwas purged with nitrogen for 20 minutes
  2. customThe cooled reaction mixture
  3. customwas partitioned between ethyl acetate (80 mL) and 1.0 M aqueous sodium hydroxide solution (80 mL)
  4. customthe organic phase separated
  5. washwashed with water (80 mL) and saturated brine (80 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a yellow syrup
  10. customThe crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 20% ethyl acetate (containing 2% methanol) in hexanes

Sources & evidence

ORD record
ord-d1a10289003a4c39a176eae0847ac34d
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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