Diisopropylamine → (2,3,4-Trimethoxy-6-methylphenyl)(5-bromo-4-trifluoromethyl-2-methoxy-3-pyridyl)methanol

HRID 242425Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 242425
C([Li])CCC.C(NC(C)C)(C)C.[Br:13][C:14]1[C:15]([C:22]([F:25])([F:24])[F:23])=[CH:16][C:17]([O:20][CH3:21])=[N:18][CH:19]=1.FC(F)(F)C1C=CN=C(OC)C=1.BrC1C(C(F)(F)F)=C([Li])C(OC)=NC=1.FC(F)(F)C1C=CN=C(OC)C=1[Li].[CH3:65][O:66][C:67]1[C:74]([O:75][CH3:76])=[C:73]([O:77][CH3:78])[CH:72]=[C:71]([CH3:79])[C:68]=1[CH:69]=[O:70]>O1CCCC1.O>[CH3:65][O:66][C:67]1[C:74]([O:75][CH3:76])=[C:73]([O:77][CH3:78])[CH:72]=[C:71]([CH3:79])[C:68]=1[CH:69]([C:16]1[C:17]([O:20][CH3:21])=[N:18][CH:19]=[C:14]([Br:13])[C:15]=1[C:22]([F:25])([F:23])[F:24])[OH:70]

Komponenten

10

Edukt 7

HCID 7912DiisopropylamineHCID 896832,3,4-Trimethoxy-6-methylbenzaldehydeHCID 18539797Pyridine, 2-methoxy-4-(trifluoromethyl)-HCID 230826445-Bromo-2-methoxy-4-(trifluoromethyl)pyridineHCID 178418339ButyllithiumHCID 178506747HCID 178506747, VerbindungHCID 178506768HCID 178506768, Verbindung

Produkt 1

HCID 23082661(2,3,4-Trimethoxy-6-methylphenyl)(5-bromo-4-trifluoromethyl-2-methoxy-3-pyridyl)methanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

17.1 ml of n-butyllithium (1.57 mol/l hexane solution) was dropwise added at 0° C. to a solution having 3.80 ml (27.1 mmol) of diisopropylamine dissolved in 50 ml of tetrahydrofuran, followed by stirring for 30 minutes. The solution was cooled to −78° C., and a solution having 5.81 g of the mixture of 5-bromo-4-trifluoromethyl-2-methoxypyridine and 4-trifluoromethyl-2-methoxypyridine (molar ratio 55:45) obtained in Step (c) dissolved in 10 ml of tetrahydrofuran was added, followed by stirring for 45 minutes to prepare a mixture of 5-bromo-4-trifluoromethyl-2-methoxy-3-pyridyllithium and 4-trifluoromethyl-2-methoxy-3-pyridyllithium. A solution having 5.51 g (26.2 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 15 ml of tetrahydrofuran was added, followed by stirring for 1 hour. Water was added to the mixture to terminate the reaction, and tetrahydrofuran was distilled off under reduced pressure. After extraction with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 5.02 g of (2,3,4-trimethoxy-6-methylphenyl)(5-bromo-4-trifluoromethyl-2-methoxy-3-pyridyl)methanol.

Aufarbeitung

  1. customobtained in Step (c)
  2. additionwas added
  3. stirringby stirring for 45 minutes
  4. customto prepare
  5. additionwas added
  6. stirringby stirring for 1 hour
  7. customto terminate
  8. customthe reaction, and tetrahydrofuran
  9. distillationwas distilled off under reduced pressure
  10. extractionAfter extraction with ethyl acetate
  11. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  12. filtrationsubjected to filtration
  13. distillationthe solvent was distilled off under reduced pressure
  14. customThe crude product was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-b11be89ef4134dc1bfe1557c050cb13b
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653113B2

Notizen zur Reaktion

Wird geladen…