1-[(4-fluorophenyl)methyl]-1H-1,3-benzodiazole → [1-[2-(4-Methoxyphenyl)ethyl]-4-piperidinyl]methanone

HRID 1647046Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1647046
FC1C=CC(CN2C3C=CC=CC=3N=C2)=CC=1.C([Li])CCC.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][N:33]2[CH2:38][CH2:37][CH:36]([C:39](OC)=[O:40])[CH2:35][CH2:34]2)=[CH:27][CH:26]=1>C1COCC1.CCCCCC>[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][N:33]2[CH2:38][CH2:37][CH:36]([CH:39]=[O:40])[CH2:35][CH2:34]2)=[CH:27][CH:26]=1

Komponenten

6

Edukt 3

HCID 7555721-[(4-fluorophenyl)methyl]-1H-1,3-benzodiazoleHCID 108695871-[2-(4-Methoxyphenyl)ethyl]-4-piperidinecarboxylic acid, methyl esterHCID 178418339Butyllithium

Produkt 1

HCID 53767224[1-[2-(4-Methoxyphenyl)ethyl]-4-piperidinyl]methanone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8058HexaneLösungsmittel

Versuchsvorschrift

To a stirred, -78° C., solution of 1-[(4-fluorophenyl)methyl]-1H-benzimidazole (1.13 g, 5.00×10-3 mole) and dry THF (12 ml) under argon was added a 2.5 molar hexane solution of n-butyl lithium (2.1 ml, 5.25×10-3 mole). After 15-20 minutes at -78° C., a solution of 1-[2-(4-methoxyphenyl)ethyl]-4-piperidinecarboxylic acid, methyl ester (1.39 g, 5.01×10-3 mole) and dry THF (6 ml) was added dropwise via syringe. After 5-10 minutes, the cooling bath was removed and the reaction was allowed to warm. After ca. 30 minutes, the reaction was quenched by the addition of saturated aqueous NH4Cl. The reaction was transferred to a separatory funnel where the aqueous mixture was extracted two times with ethyl acetate. The ethyl acetate extracts were combined, washed with saturated aqueous NaCl, and dried over anhydrous Na2SO4. The drying agent was removed by filtration and the filtrate was evaporated at reduced pressure affording a viscous oil. This was purified by a combination of flash chromatography (ethyl acetate) and crystallization (cyclohexane) affording 1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl][1-[2-(4methoxyphenyl)ethyl]-4-piperidinyl]methanone as off white matted needles: 0.90 g (38%), m.p. 109-111° C.

Aufarbeitung

  1. waitAfter 5-10 minutes
  2. customthe cooling bath was removed
  3. temperatureto warm
  4. waitAfter ca. 30 minutes
  5. customthe reaction was quenched by the addition of saturated aqueous NH4Cl
  6. customThe reaction was transferred to a separatory funnel
  7. extractionwhere the aqueous mixture was extracted two times with ethyl acetate
  8. washwashed with saturated aqueous NaCl
  9. dry with materialdried over anhydrous Na2SO4
  10. customThe drying agent was removed by filtration
  11. customthe filtrate was evaporated at reduced pressure
  12. customaffording a viscous oil
  13. customThis was purified by a combination of flash chromatography (ethyl acetate) and crystallization (cyclohexane)

Quellen und Nachweise

ORD-Eintrag
ord-4ef6746ae3814754b098e4d8bafbb05b
Quelldatensatz
uspto-grants-1993_01
Patentnummer
US05182399

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