Acetaldehyde → tert-butyl 4-(4-(1-hydroxyethyl)-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

HRID 2088937

Reaktionsgleichung

Reaktionsgleichung von HRID 2088937
I[C:2]1[N:3]=[C:4]([CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[N:5]([CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:6]=1.C([Li])CCC.[CH:32](=[O:34])[CH3:33]>O1CCCC1>[OH:34][CH:32]([C:2]1[N:3]=[C:4]([CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[N:5]([CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:6]=1)[CH3:33]

Komponenten

5

Edukt 3

HCID 177AcetaldehydeHCID 67112018Tert-butyl 4-[4-iodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylateHCID 178418339Butyllithium

Produkt 1

HCID 67955049tert-butyl 4-(4-(1-hydroxyethyl)-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-70 °C

Versuchsvorschrift

Combine tert-butyl 4-(4-iodo-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (40.00 g, 82.63 mmol) and tetrahydrofuran (600 mL). Cool to −70° C. under nitrogen. Add 2.5 M n-butyllithium in hexanes (67.76 mL, 2.1 eq) dropwise. Add acetaldehyde (23.22 mL, 5.0 eq) and stir for 15 minutes. Quench over aqueous saturated ammonium chloride (75 mL). Separate the layers. Wash the aqueous phase with methyl tert-butyl ether. Wash the organics with water and aqueous saturated sodium chloride. Dry the organics over anhydrous magnesium sulfate, filter, and concentrate in vacuo. Dissolve in ethanol. Add 85% aqueous phosphoric acid dropwise to achieve a suspension. Stir the mixture overnight at room temperature. Filter and dry the resulting off-white solid under vacuum to give tert-butyl 4-(4-(1-hydroxyethyl)-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate; phosphoric acid (28.00 g, 69%). MS (ES) m/z=393 [M]+.

Aufarbeitung

  1. customQuench over aqueous saturated ammonium chloride (75 mL)
  2. customSeparate the layers
  3. washWash the aqueous phase with methyl tert-butyl ether
  4. washWash the organics with water and aqueous saturated sodium chloride
  5. dry with materialDry the organics over anhydrous magnesium sulfate
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. dissolutionDissolve in ethanol
  9. additionAdd 85% aqueous phosphoric acid dropwise
  10. filtrationFilter
  11. customdry the resulting off-white solid under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-e177ecdbbf88405fa3deb962f9f86152
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436002B2

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