Triisopropyl borate → (2-(Pyridin-4-yl)-4-(trifluoromethyl)phenyl)boronic acid

HRID 2172294Notes

Reaction equation

HRID 2172294 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:12]1[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=1.[B:18](OC(C)C)([O:23]C(C)C)[O:19]C(C)C.C([Li])CCC>CCOCC>[N:15]1[CH:16]=[CH:17][C:12]([C:3]2[CH:4]=[C:5]([C:8]([F:11])([F:10])[F:9])[CH:6]=[CH:7][C:2]=2[B:18]([OH:23])[OH:19])=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 21531Triisopropyl borateHCID 866873404-(2-Bromo-5-(trifluoromethyl)phenyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 86687341(2-(Pyridin-4-yl)-4-(trifluoromethyl)phenyl)boronic acidYield 63.6%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

A 250-mL round bottom flask was charged with 4-(2-bromo-5-(trifluoromethyl)phenyl)pyridine (0.242 g, 0.801 mmol), Ether (6.16 ml), and triisopropyl borate (0.223 ml, 0.961 mmol). The flask was cooled to −78° C. for 10 minutes, after which butyllithium (2.5M in hexanes) (0.385 ml, 0.961 mmol) was added dropwise. After 30 minutes the dry-ice bath was removed, and 2N aq NaOH (10 mL), and the resulting biphasic mixture was stirred vigorously. After 1 h, the mixture was diluted with water, and the layers separated. The ether was then extracted with water (×2) and the water layers were combined, and washed with ether. The ether layers were back-extracted once more, and all aqueous layers combined and neutralized to ˜pH=7 with 1N aq HCl to give a clear solution. The aqueous was extracted with DCM (×3) and the combined organics were dried over sodium sulfate, filtered and concentrated. The dried residue was taken up in DCM, and concentrated to give (2-(pyridin-4-yl)-4-(trifluoromethyl)phenyl)boronic acid (0.136 g, 0.509 mmol, 63.6% yield) as an off-white solid. [M+H]+=268.1

Workup

  1. customAfter 30 minutes the dry-ice bath was removed
  2. additionthe mixture was diluted with water
  3. customthe layers separated
  4. extractionThe ether was then extracted with water (×2)
  5. washwashed with ether
  6. extractionThe ether layers were back-extracted once more
  7. customto give a clear solution
  8. extractionThe aqueous was extracted with DCM (×3)
  9. dry with materialthe combined organics were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-f9138429a1524d4382056f0ee1f929ae
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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