1,4-Dioxane → 3-(3,5-Difluoro-pyridin-2-yl)-4-fluorophenylboronic acid

HRID 2184020Notes

Reaction equation

HRID 2184020 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:16])=[C:6]([C:8]2[C:13]([F:14])=[CH:12][C:11]([F:15])=[CH:10][N:9]=2)[CH:7]=1.[B:17]1(B2OCC(C)(C)CO2)[O:22]CC(C)(C)C[O:18]1.O1CCOCC1.C([O-])(=O)C.[K+]>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].CS(C)=O>[F:16][C:5]1[CH:4]=[CH:3][C:2]([B:17]([OH:22])[OH:18])=[CH:7][C:6]=1[C:8]1[C:13]([F:14])=[CH:12][C:11]([F:15])=[CH:10][N:9]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 116808232-(5-Bromo-2-fluorophenyl)-3,5-difluoropyridine

Product 1

HCID 116374193-(3,5-Difluoro-pyridin-2-yl)-4-fluorophenylboronic acidYield 94.3%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
85 °C

Procedure

To 2-(5-bromo-2-fluorophenyl)-3,5-difluoropyridine (0.746 g, 2.59 mmol), and bis(neopentyl glycolato)diborane (0.704 g) was added dry 1,4-dioxane (9 ml) and dry dimethylsulfoxide (1.1 ml) followed by potassium acetate (0.542 g) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.080 g). The mixture was thoroughly degassed with nitrogen and then stirred at 85° C. for 24 h. On cooling to ambient temperature 1N aqueous sodium hydroxide (24 ml) was added and the mixture stirred for 30 min. Diethyl ether was added and the aqueous phase separated and washed with diethyl ether. The organics were discarded. The aqueous phase was filtered then acidified to pH 5 by addition of 2N aqueous hydrochloric acid (12 ml). The resulting solid was collected by filtration, washed with water and dried in vacuo at 60° C. to afford 4-fluoro-3-(3,5-difluoropyridin-2-yl)phenylboronic acid (0.618 g) as a colourless solid: δH (400 MHz, DMSO) 8.69 (1H, d, J 2), 8.21 (2H, s), 7.94-8.14 (3H, m), 7.34 (1H, dd, J 11 and 8).

Workup

  1. customThe mixture was thoroughly degassed with nitrogen
  2. temperatureOn cooling to ambient temperature 1N aqueous sodium hydroxide (24 ml)
  3. additionwas added
  4. stirringthe mixture stirred for 30 min
  5. additionDiethyl ether was added
  6. customthe aqueous phase separated
  7. washwashed with diethyl ether
  8. filtrationThe aqueous phase was filtered
  9. additionthen acidified to pH 5 by addition of 2N aqueous hydrochloric acid (12 ml)
  10. filtrationThe resulting solid was collected by filtration
  11. washwashed with water
  12. customdried in vacuo at 60° C.

Sources & evidence

ORD record
ord-b23f19faae964bec8ab89dc34d0ebfa4
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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