Potassium Acetate → HCID 22285265, compound

HRID 586260Notes

Reaction equation

HRID 586260 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:14])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[CH:7]=1.C([O-])(=O)C.[K+].[B:20]1(B2OC(C)(C)C(C)(C)O2)[O:24]C(C)(C)C(C)(C)[O:21]1>O1CCOCC1.CS(C)=O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[F:14][C:5]1[CH:4]=[CH:3][C:2]([B:20]([OH:24])[OH:21])=[CH:7][C:6]=1[C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1

Participants

7

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 22285319HCID 22285319, compound

Product 1

HCID 22285265HCID 22285265, compoundYield 46.1%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-(5-bromo-2-fluorophenyl)pyridine (3.8 g, 15.1 mmol), potassium acetate (2.96 g, 30.1 mmol) and bis(pinacolato)diboron (4.21 g, 16.6 mmol) in 1,4-dioxane (50 ml) and dimethylsulfoxide (1 ml) was degassed with nitrogen for 1 h. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (370 mg, 0.5 mmol) was added and the mixture heated at 90° C. for 18 h. The reaction was cooled to ambient temperature, filtered and the filter-cake washed with diethyl ether. The filtrate was evaporated to dryness and the residue stirred with ice-cold 2 N sodium hydroxide (100 ml) for 20 min. The aqueous mixture was filtered and the filtrate washed with diethyl ether (2×75 ml). The organics were discarded and the aqueous phase cooled to 0° C. before lowering the pH to 8 by addition of 36% hydrochloric acid. The resulting solid was collected by filtration and triturated with diethyl ether to afford 4-fluoro-3-(pyridin-4-yl)benzeneboronic acid as a buff-coloured solid (1.51 g, 46%): 1H NMR (360 MHz, DMSO-d6) δ 7.34 (1H, dd, J 11, 8 Hz), 7.61 (2H, d, J 5 Hz), 7.88-7.92 (1H, m), 8.05 (1H, dd, J 8, 1 Hz), 8.26 (2H, s), 8.70 (2H, d, J 5 Hz); MS (ES+) m/z 218 [M+H]+. The aqueous filtrate was extracted with diethyl ether. The organic phase was washed with water, brine, dried (MgSO4), filtered and evaporated to afford 4-[2-fluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]pyridine as a dark oil (1.28 g, 29%) that solidified on standing for a few days: 1H NMR (360 MHz, CDCl3) δ 1.36 (12H, s), 7.19 (1H, dd, J 11, 8 Hz), 7.50-7.53 (2H, m), 7.82-7.87 (1H, m), 7.93 (1H, dd, J 8, 1 Hz), 8.67 (2H, dd, J 4, 1 Hz); MS (ES+) m/z 300 [M+H]+.

Workup

  1. customwas degassed with nitrogen for 1 h
  2. temperatureThe reaction was cooled to ambient temperature
  3. filtrationfiltered
  4. washthe filter-cake washed with diethyl ether
  5. customThe filtrate was evaporated to dryness
  6. filtrationThe aqueous mixture was filtered
  7. washthe filtrate washed with diethyl ether (2×75 ml)
  8. temperaturethe aqueous phase cooled to 0° C.
  9. additionby addition of 36% hydrochloric acid
  10. filtrationThe resulting solid was collected by filtration
  11. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-9664dc9915b54e85b2054c3fa6223580
Source dataset
uspto-grants-2005_08
Patent number
US06936608B2

Reaction notes

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