Veratrole → (2,3-Dimethoxyphenyl)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol

HRID 53192Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 53192
[C:1]1([O:9][CH3:10])[C:2](=[CH:5][CH:6]=[CH:7][CH:8]=1)[O:3][CH3:4].[Li]CCCC.[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][N:25]2[CH2:30][CH2:29][CH:28]([CH:31]=[O:32])[CH2:27][CH2:26]2)=[CH:19][CH:18]=1>C1COCC1.CCCCCC>[CH3:4][O:3][C:2]1[C:1]([O:9][CH3:10])=[CH:8][CH:7]=[CH:6][C:5]=1[CH:31]([CH:28]1[CH2:29][CH2:30][N:25]([CH2:24][CH2:23][C:20]2[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=2)[CH2:26][CH2:27]1)[OH:32]

Komponenten

6

Edukt 3

HCID 7043VeratroleHCID 15392119HCID 15392119, VerbindungHCID 178418339Butyllithium

Produkt 1

HCID 60858(2,3-Dimethoxyphenyl)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a stirred solution of veratrole (0.93 g, 6.7 mmol) in THF (20 mL) under argon at 0° C. was added n-BuLi (2.7 mL of a 2.5M solution in hexane, 6.75 mmol). After stirring 2.5 h, the solution was cooled to -78° C. and treated with 1-[2-(4-fluorophenyl)ethyl]-4-piperidinecarboxaldehyde (1.30 g, 5.5 mmol) in THF (25 mL) via an addition funnel. The cooling bath was removed and the solution was allowed to stir for 2 hours. Water was added, the layers separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered, and chromatographed on silica gel, eluting with acetone. The appropriate fractions were combined and evaporated to afford a white solid. The solid was recrystallized from hexane to afford racemic α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol as shiny white needles, m.p. 126°-127° C. Anal. Calcd for C22H28FNO3 : C, 70.75; H, 7.56; N, 3.75. Found: C, 70.87; H, 7.65; N, 3.68.

Aufarbeitung

  1. customThe cooling bath was removed
  2. stirringto stir for 2 hours
  3. additionWater was added
  4. customthe layers separated
  5. extractionthe aqueous layer was extracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customchromatographed on silica gel
  10. washeluting with acetone
  11. customevaporated
  12. customto afford a white solid
  13. customThe solid was recrystallized from hexane

Quellen und Nachweise

ORD-Eintrag
ord-fd655b6905464284a6bb5dd9fecd8a75
Quelldatensatz
uspto-grants-1997_04
Patentnummer
US05618824

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