Triisopropyl borate → (5-(((tert-Butyldimethylsilyl)oxy)methyl)pyridin-3-yl)boronic acid

HRID 1364070

Reaktionsgleichung

Reaktionsgleichung von HRID 1364070
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[CH:7]=1.[B:17](OC(C)C)([O:22]C(C)C)[O:18]C(C)C.C([Li])CCC.[Cl-].[NH4+]>C1COCC1.O>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:11])[CH3:12])[CH:7]=1.[Si:10]([O:9][CH2:8][C:6]1[CH:7]=[C:2]([B:17]([OH:22])[OH:18])[CH:3]=[N:4][CH:5]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Komponenten

8

Edukt 4

HCID 21531Triisopropyl borateHCID 25517Ammonium ChlorideHCID 219840913-Bromo-5-(((tert-butyldimethylsilyl)oxy)methyl)pyridineHCID 178418339Butyllithium

Produkt 2

HCID 219840913-Bromo-5-(((tert-butyldimethylsilyl)oxy)methyl)pyridineHCID 21984252(5-(((tert-Butyldimethylsilyl)oxy)methyl)pyridin-3-yl)boronic acidAusbeute 143,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

For example 373, the solvent was removed by vacuum centrifugation. Glacial acetic acid (3 mL), THF (1 mL), and deionized water (1 mL), and the reaction was heated at 60° C. overnight. 3-Bromo-5-(tert-butyldimethylsilanyloxymethyl)pyridine was prepared according to the published procedure (Zhang, N. et al, J. Med. Chem., 45, 2832-2840 (2002)). Under a nitrogen atmosphere, a solution of 3-bromo-5-(tert-butyldimethylsilanyloxymethyl)pyridine (28.70 g, 94.94 mmol) and triisopropyl borate (26.3 mL, 114 mmol) in dry THF was cooled to −70° C. n-Butyllithium (45.6 mL, 114 mmol) was added dropwise over a period of 1.5 hours. The reaction was stirred for an additional 30 minutes and then allowed to warm to −20° C. Dilute aqueous ammonium chloride was added, and the mixture was allowed to warm to ambient temperature. The aqueous layer was separated and extracted with diethyl ether. The combined organic fractions were concentrated under reduced pressure, and methanol was added to the resulting oil. A solid formed, which was stirred with water for two days, isolated by filtration, and dried under reduced pressure to provide 18.19 g of 5-(tert-butyldimethylsilanyloxymethyl)pyridine-3-boronic acid as a white solid.

Aufarbeitung

  1. customFor example 373, the solvent was removed by vacuum centrifugation
  2. additionwas added dropwise over a period of 1.5 hours
  3. temperatureto warm to −20° C
  4. temperatureto warm to ambient temperature
  5. customThe aqueous layer was separated
  6. extractionextracted with diethyl ether
  7. concentrationThe combined organic fractions were concentrated under reduced pressure, and methanol
  8. additionwas added to the resulting oil
  9. customA solid formed
  10. customisolated by filtration
  11. customdried under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-1e7e5f626da24917999d73194a4649c2
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07888349B2

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