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

HRID 586279Notes

Reaction equation

HRID 586279 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)diboron (0.704 g) was added dry 1,4-dioxane (9 ml) and dry dimethylsulfoxide (1.1 ml), followed by dry 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 room temperature, 1 N aqueous sodium hydroxide (24 ml) was added, and the mixture stirred for 0.5 h. Diethyl ether was added and the aqueous phase was separated and washed with diethyl ether. The organic extracts were washed with water, and the combined aqueous phases were filtered, then acidified to pH 5 by addition of 2 N aqueous hydrochloric acid (12 ml). The resulting solid was collected by filtration, washed with water, and dried in vacuo at 60° C. to afford 0.618 g of 4-fluoro-3-(3,5-difluoropyridin-2-yl)phenylboronic acid as a colourless solid: 1H NMR (400 MHz, DMSO-d6) δ 8.69 (1H, d, J 2.3 Hz), 8.21 (2H, s), 7.94-8.14 (3H, m), 7.34 (1H, dd, J 8.2, 10.6 Hz).

Workup

  1. customThe mixture was thoroughly degassed with nitrogen
  2. temperatureOn cooling to room temperature
  3. addition1 N aqueous sodium hydroxide (24 ml) was added
  4. stirringthe mixture stirred for 0.5 h
  5. additionDiethyl ether was added
  6. customthe aqueous phase was separated
  7. washwashed with diethyl ether
  8. washThe organic extracts were washed with water
  9. filtrationthe combined aqueous phases were filtered
  10. additionacidified to pH 5 by addition of 2 N aqueous hydrochloric acid (12 ml)
  11. filtrationThe resulting solid was collected by filtration
  12. washwashed with water
  13. customdried in vacuo at 60° C.

Sources & evidence

ORD record
ord-1fac1613449049858e431aa89bfc3de6
Source dataset
uspto-grants-2005_08
Patent number
US06936608B2

Reaction notes

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