4-Methylquinoline → 2-(1-Fluorocyclopropyl)-4-(4-fluorophenyl)-4-methyl-1-quinolin-4-ylpentan-2-ol

HRID 400686Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 400686
[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[Li].[F:13][C:14]1([C:17](=[O:29])[CH2:18][C:19]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)([CH3:21])[CH3:20])[CH2:16][CH2:15]1>C1COCC1>[F:13][C:14]1([C:17]([OH:29])([CH2:18][C:19]([C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)([CH3:21])[CH3:20])[CH2:1][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[CH:4][CH:3]=2)[CH2:15][CH2:16]1

Komponenten

5

Edukt 3

HCID 102854-Methylquinoline2×HCID 3028194LithiumHCID 600264051-(1-Fluorocyclopropyl)-3-(4-fluorophenyl)-3-methylbutan-1-one

Produkt 1

HCID 574481072-(1-Fluorocyclopropyl)-4-(4-fluorophenyl)-4-methyl-1-quinolin-4-ylpentan-2-olAusbeute 24,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of 4-methylquinoline (69 mg, 0.482 mmol) in THF cooled on dry ice/acetone was added 0.4 mL of lithium dilsopropylamide (1.5 M in hexanes). The mixture was placed in a cold bath at −20° C. to −30° C. for 15 minutes and then cooled to −78° C. 1-(1-Fluorocyclopropyl)-3-(4-fluorophenyl)-3-methylbutan-1-one (49 mg, 0.206 mmol) was added dropwise as a solution in 0.5 mL of THF. The cold bath was then removed and the mixture stirred for 1 hour. The reaction was quenched by addition of 0.5 mL of water and diluted with ethyl acetate. The organic phase was separated, washed with water, dried, filtered, and the solvent evaporated in vacuo. Fractionation of the residue by preparative layer chromatography (developer: ethyl acetate-hexanes (2:1)) gave the title compound (0.019 g, 24% yield) (slightly less polar than lepidine) as an oil that crystallized on standing in hexanes, m.p. 152° C.-155° C.

Aufarbeitung

  1. customThe cold bath was then removed
  2. customThe reaction was quenched by addition of 0.5 mL of water
  3. additiondiluted with ethyl acetate
  4. customThe organic phase was separated
  5. washwashed with water
  6. customdried
  7. filtrationfiltered
  8. customthe solvent evaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-7f0814b7367e4ca19d7aeaa04d8b85f1
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08741897B2

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