Triisopropyl borate → 5-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-ylboronic acid

HRID 1812307

Reaction equation

HRID 1812307 reaction equation
C([Li])CCC.[Si:6]([O:13][CH2:14][C:15]([C:18]1[CH:19]=[CH:20][C:21]([F:24])=[N:22][CH:23]=1)([CH3:17])[CH3:16])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[B:25](OC(C)C)([O:30]C(C)C)[O:26]C(C)C>C1COCC1>[Si:6]([O:13][CH2:14][C:15]([C:18]1[CH:19]=[C:20]([B:25]([OH:30])[OH:26])[C:21]([F:24])=[N:22][CH:23]=1)([CH3:17])[CH3:16])([C:9]([CH3:10])([CH3:11])[CH3:12])([CH3:8])[CH3:7]

Participants

5

Reactant 3

HCID 21531Triisopropyl borateHCID 666006945-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridineHCID 178418339Butyllithium

Product 1

HCID 665999945-(1-(Tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-ylboronic acidYield 108%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (1.66 M in hexane) (Aldrich, St. Louis, Mo.; 0.429 mL, 0.712 mmol) was added (dropwise over 1 min) to a solution of 5-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridine (183.5 mg, 0.647 mmol) in THF (3.3 mL) at −78° C., and the resulting yellow solution was stirred at −78° C. for 1 h. Tri-isopropyl borate (Aldrich, St. Louis, Mo.; 0.179 mL, 0.777 mmol) was then added, and the resulting mixture was stirred at −78° C. for 1 h. The reaction mixture was subsequently partitioned between EtOAc (50 mL) and water (30 mL) (1N HCl (about 200 μL) was added to bring the pH of the aqueous layer to 6.5). The organic layer was separated, and the aqueous layer was extracted with EtOAc (30 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to provide 5-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluoropyridin-3-ylboronic acid (228.0 mg, 0.697 mmol, 108% yield) as a colorless oil. m/z (ESI, +ve) 328.3 (M+H)+.

Workup

  1. stirringthe resulting mixture was stirred at −78° C. for 1 h
  2. customThe reaction mixture was subsequently partitioned between EtOAc (50 mL) and water (30 mL) (1N HCl (about 200 μL)
  3. additionwas added
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc (30 mL)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c3b398b82fe64ffeafbde30457bba527
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Linked notes

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