Triisopropyl borate → 2-Fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-ylboronic acid

HRID 1811852

Reaktionsgleichung

Reaktionsgleichung von HRID 1811852
Br[C:2]1[C:3]([F:19])=[N:4][CH:5]=[C:6]([CH2:8][O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH:7]=1.C([Li])CCC.[B:25](OC(C)C)([O:30]C(C)C)[O:26]C(C)C>C1(C)C=CC=CC=1>[F:19][C:3]1[C:2]([B:25]([OH:30])[OH:26])=[CH:7][C:6]([CH2:8][O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)=[CH:5][N:4]=1

Komponenten

5

Edukt 3

HCID 21531Triisopropyl borateHCID 595482913-Bromo-2-fluoro-5-((4-methoxybenzyloxy)methyl)pyridineHCID 178418339Butyllithium

Produkt 1

HCID 595482052-Fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-ylboronic acidAusbeute 96,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

3-Bromo-2-fluoro-5-((4-methoxybenzyloxy)methyl)pyridine (1.615 g, 4.952 mmol) was dissolved in PhMe (25.0 mL) and the reaction flask was cooled under nitrogen in a dry ice/acetone bath. Then, n-butyllithium solution (Fluka, Buchs, Switzerland, 1.6 M in hexane, 3.7 mL, 5.9 mmol) was added via syringe, turning the solution yellow. The reaction was stirred at −78° C. for 45 minutes and then triisopropyl borate (Alfa Aesar, Ward Hill, Mass. 98+%, 1.7 mL, 7.2 mmol) was added via syringe. The reaction was allowed to slowly warm up to room temperature, and after 90 minutes, the dry ice/acetone bath was removed. After another 25 minutes, the reaction was quenched with water and diluted with 10:1 DCM/MeOH. The biphasic solution was treated with 5 N HCl to lower the pH of the aqueous phase from 9 to about 4, and the aqueous phase extracted with 10:1 DCM/MeOH. The organic extracts were concentrated and dried under high vacuum in water bath (about 45° C.-60° C.), and then the solid was washed with Et2O and dried again under high vacuum at room temperature over the weekend to afford 2-fluoro-5-((4-methoxybenzyloxy)methyl)pyridin-3-ylboronic acid (1.389 g, 68% purity, 66% yield). MS (ESI pos. ion) m/z 292 (M+H)+.

Aufarbeitung

  1. temperaturethe reaction flask was cooled under nitrogen in a dry ice/acetone bath
  2. temperatureto slowly warm up to room temperature
  3. waitafter 90 minutes
  4. customthe dry ice/acetone bath was removed
  5. waitAfter another 25 minutes
  6. customthe reaction was quenched with water
  7. additiondiluted with 10:1 DCM/MeOH
  8. additionThe biphasic solution was treated with 5 N HCl
  9. extractionthe aqueous phase extracted with 10:1 DCM/MeOH
  10. concentrationThe organic extracts were concentrated
  11. dry with materialdried under high vacuum in water bath (about 45° C.-60° C.)
  12. washthe solid was washed with Et2O
  13. customdried again under high vacuum at room temperature over the weekend

Quellen und Nachweise

ORD-Eintrag
ord-3403bd052384461db840956175cc4652
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362241B2

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