Potassium Carbonate → HCID 86718615, compound

HRID 1480649Notes

Reaction equation

HRID 1480649 reaction equation
Br[C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[N:3]=1.[F:16][C:17]([F:28])([F:27])[C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][N:19]=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>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([C:4]2[N:3]=[C:2]([C:21]3[CH:20]=[N:19][C:18]([C:17]([F:28])([F:27])[F:16])=[CH:23][CH:22]=3)[C:7]([OH:8])=[CH:6][CH:5]=2)=[CH:10][CH:11]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 251342782-(Trifluoromethyl)pyridine-5-boronic AcidHCID 86718614HCID 86718614, compound

Product 1

HCID 86718615HCID 86718615, compoundYield 60%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

A mixture of 2-bromo-6-(4-chlorophenyl)pyridin-3-ol (0.319 g, 1.12 mmol), 2-(trifluoromethyl)pyridine-5-boronic acid [purchased from Frontier Scientific] (277.8 mg, 1.46 mmol) and potassium carbonate (386.7 mg, 2.798 mmol) in dimethoxyethane (15 mL) and water (5 mL) was purged with nitrogen for 20 minutes. Tetrakis(triphenylphosphine)palladium(0) (64.7 mg, 0.056 mmol) was added and the reaction mixture heated to 80° C. in a sealed vial for 15 hours. The cooled reaction mixture was partitioned between ethyl acetate (50 mL) and saturated aqueous ammonium chloride solution (50 mL), the organic phase separated, washed with water (50 mL) and saturated brine (50 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give a yellow solid. The crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 50% ethyl acetate in hexanes to give 6-(4-chlorophenyl)-6′-(trifluoromethyl)-[2,3′-bipyridin]-3-ol (0.234 g, 60% yield) as a cream solid.

Workup

  1. customwas purged with nitrogen for 20 minutes
  2. customThe cooled reaction mixture
  3. customwas partitioned between ethyl acetate (50 mL) and saturated aqueous ammonium chloride solution (50 mL)
  4. customthe organic phase separated
  5. washwashed with water (50 mL) and saturated brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a yellow solid
  10. customThe crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-7b3f317724a644ad86ae721fa56d38c1
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

Loading…