Cesium carbonate → HCID 117858275, compound

HRID 1486312Notes

Reaction equation

HRID 1486312 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[CH:3]=1.[CH:18]1(B2OC(C)(C)C(C)(C)O2)[CH2:20][CH2:19]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O.O1CCOCC1>[CH:18]1([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH2:9][C:10]3[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=3[F:17])[CH:3]=2)[CH2:20][CH2:19]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27580152-Cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 117858781HCID 117858781, compound

Product 1

HCID 117858275HCID 117858275, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 500 mg (1.66 mmol) of 4-bromo-2-[(2,6-difluorobenzyl)oxy]pyridine (Example 145A), 365 μl (2.0 mmol) of 2-cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 139 mg (0.17 mmol) of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride-dichloromethane complex and 1.63 g (5.0 mmol) of caesium carbonate in 0.5 ml of water and 4 ml of dioxane was degassed with argon for 5 min and stirred in a sealed tube at 100° C. for 2 h. The reaction mixture was cooled to room temperature and the residue was partitioned between ethyl acetate and water. The organic phase was removed and washed with saturated aqueous sodium chloride solution, dried over sodium sulphate, filtered and concentrated. The residue was purified by chromatography on silica gel (40 g silica gel cartridge, mobile phase: methanol/ethyl acetate, gradient 0% to 25%). This gave 350 mg of the target compound (80% of theory).

Workup

  1. customwas degassed with argon for 5 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customthe residue was partitioned between ethyl acetate and water
  4. customThe organic phase was removed
  5. washwashed with saturated aqueous sodium chloride solution
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (40 g silica gel cartridge, mobile phase: methanol/ethyl acetate, gradient 0% to 25%)

Sources & evidence

ORD record
ord-eed2624b4514432c838973a85d61d28e
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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