Hexane → (6-tert-Butylpyridin-3-yl)boronic acid

HRID 1480601Notes

Reaction equation

HRID 1480601 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([CH3:11])([CH3:10])[CH3:9])=[N:6][CH:7]=1.C([O:15][B:16](OC(C)C)[O:17]C(C)C)(C)C.C([Li])CCC.CCCCCC>O1CCCC1.CCOCC>[C:8]([C:5]1[CH:4]=[CH:3][C:2]([B:16]([OH:17])[OH:15])=[CH:7][N:6]=1)([CH3:11])([CH3:10])[CH3:9]

Participants

7

Reactant 4

HCID 8058HexaneHCID 21531Triisopropyl borateHCID 210413085-Bromo-2-tert-butylpyridineHCID 178418339Butyllithium

Product 1

HCID 53407669(6-tert-Butylpyridin-3-yl)boronic acidYield 61%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-bromo-2-(tert-butyl)pyridine (1 g, 4.67 mmol) and triisopropylborate (1.29 mL, 5.60 mmol) in anhydrous tetrahydrofuran (10 mL) at −78° C. under nitrogen was added dropwise a solution of n-butyl lithium in hexane (2.5 M, 2.06 mL, 5.14 mmol). The reaction was stirred at −78° C. for 2½ hours then allowed to warm slowly to −10° C. over 1 hour. The reaction was quenched by the addition of water (10 mL) and the tetrahydrofuran removed under reduced pressure. The resulting aqueous suspension was diluted with water (30 mL) and washed with ether (30 mL). The aqueous phase was acidified to pH 6 by the addition of acetic acid and the resulting milky suspension extracted with ether (2×20 mL). The combined organic extracts were washed with saturated brine (2×50 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give a white foam. Ether (5 mL) and hexanes (40 mL) were added and the resulting suspension stirred vigorously for 30 minutes then filtered to give 2-(tert-butyl)pyridine-5-boronic acid (0.5093 g, 61% yield) as a white solid.

Workup

  1. temperatureto warm slowly to −10° C. over 1 hour
  2. customThe reaction was quenched by the addition of water (10 mL)
  3. customthe tetrahydrofuran removed under reduced pressure
  4. additionThe resulting aqueous suspension was diluted with water (30 mL)
  5. washwashed with ether (30 mL)
  6. additionThe aqueous phase was acidified to pH 6 by the addition of acetic acid
  7. extractionthe resulting milky suspension extracted with ether (2×20 mL)
  8. washThe combined organic extracts were washed with saturated brine (2×50 mL)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto give a white foam
  13. stirringthe resulting suspension stirred vigorously for 30 minutes
  14. filtrationthen filtered

Sources & evidence

ORD record
ord-9936eedd2b8744128d41c772b828b0cc
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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