Benzaldehyde → (3S,4R)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine

HRID 424733Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 424733
[NH2:1][CH2:2][C@@H:3]1[C@@H:7]([F:8])[CH2:6][N:5]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:4]1.NCC1CN(C(O[CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=O)CC=1.C(=O)C1C=CC=CC=1.Cl.[OH-].[Na+]>CO>[CH2:29]([NH:1][CH2:2][C@@H:3]1[C@@H:7]([F:8])[CH2:6][N:5]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:4]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Komponenten

7

Edukt 5

HCID 240BenzaldehydeHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 230620723-Aminomethyl-1-benzyloxycarbonyl-3-pyrrolineHCID 66705221(3S,4R)-3-aminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine

Produkt 1

HCID 66704865(3S,4R)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

The mixture (310 mg) of (3S,4R)-3-aminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine and 3-aminomethyl-1-benzyloxycarbonyl-3-pyrroline was dissolved in methanol (4 mL). To this solution, molecular sieves 4A (130 mg) and then benzaldehyde (0.13 mL) were added and the mixture was stirred at room temperature for 1 hour. Subsequently, a borane/pyridine complex (0.19 mL) was added and the reaction mixture was further stirred at room temperature for 4 hours. 6 mol/L hydrochloric acid (2 mL) was then added and the mixture was stirred at room temperature for 1 hour, followed by addition of a 30% aqueous solution of sodium hydroxide to make the mixture basic. The mixture was then extracted with diethyl ether (3×10 mL) The diethyl ether layers were combined and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:methanol=10:1) to give (3S,4R)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine as a pale yellow oil (177 mg).

Aufarbeitung

  1. additionSubsequently, a borane/pyridine complex (0.19 mL) was added
  2. stirringthe reaction mixture was further stirred at room temperature for 4 hours
  3. stirringthe mixture was stirred at room temperature for 1 hour
  4. extractionThe mixture was then extracted with diethyl ether (3×10 mL) The diethyl ether layers
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:methanol=10:1)

Quellen und Nachweise

ORD-Eintrag
ord-b9286fe9582446dda0387ad775e29a48
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08106072B2

Notizen zur Reaktion

Wird geladen…