Epibromohydrin → 1-{(R*)-(4-chlorophenyl)[4-(methoxycarbonyl)phenyl]methyl}azetidin-3-ol

HRID 985467

Reaktionsgleichung

Reaktionsgleichung von HRID 985467
C(=O)([O-])O.[Na+].[NH2:6][C@@H:7]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=1)[C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=1.[CH2:25]([CH:27]1[O:29][CH2:28]1)Br>C(O)C>[Cl:24][C:21]1[CH:20]=[CH:19][C:18]([C@@H:7]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)[N:6]2[CH2:28][CH:27]([OH:29])[CH2:25]2)=[CH:23][CH:22]=1

Komponenten

5

Edukt 3

HCID 18430EpibromohydrinHCID 516892Sodium BicarbonateHCID 69635624methyl(+)-4-[(R*)-amino-(4-chlorophenyl)methyl]benzoate

Produkt 1

HCID 542067601-{(R*)-(4-chlorophenyl)[4-(methoxycarbonyl)phenyl]methyl}azetidin-3-ol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

1-{(R*)-(4-Chlorophenyl)[4-methoxycarbonyl)phenyl]methyl}azetidin-3-ol, A isomer form, may be prepared by carrying out the procedure in the following manner: 0.605 g of sodium hydrogen carbonate is added to a suspension of 2.0 g of methyl (+)-4-[(R*)-amino-(4-chlorophenyl)methyl]benzoate in 30 cm3 of ethanol followed by 0.60 cm3 of epibromohydrin. After stirring for 20 hours at 60° C., the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.06-0.200 mm, diameter 3 cm, height 35 cm), eluting under an argon pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (70/30 by volume for fractions 6 to 10 and then 60/40 for fractions 18 to 27, and then 50/50) and collecting 60-cm3 fractions. Fractions 15 to 40 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). The residue is taken up in 30 cm3 of ethanol and is then supplemented with 0.20 g of sodium hydrogen carbonate and 0.2 cm3 of epibromohydrin. After stirring for 48 hours at 20° C. and then 24 hours at 35° C., the mixture is filtered and the filtrate is concentrated to dryness at 60° C. under reduced pressure (2.7 kPa). 1.76 g of 1-{(R*)-(4-chlorophenyl)[4-(methoxycarbonyl)phenyl]methyl}azetidin-3-ol, A isomer form, are obtained in the form of a pasty solid.

Aufarbeitung

  1. custom1-{(R*)-(4-Chlorophenyl)[4-methoxycarbonyl)phenyl]methyl}azetidin-3-ol, A isomer form, may be prepared
  2. concentrationthe reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa)
  3. customThe residue is chromatographed on a silica gel column (particle size 0.06-0.200 mm, diameter 3 cm, height 35 cm)
  4. washeluting under an argon pressure of 0.5 bar
  5. additionwith a mixture of cyclohexane and ethyl acetate (70/30 by volume for fractions 6 to 10
  6. custom60/40 for fractions 18 to 27, and then 50/50) and collecting 60-cm3 fractions
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  8. stirringAfter stirring for 48 hours at 20° C.
  9. filtration24 hours at 35° C., the mixture is filtered
  10. concentrationthe filtrate is concentrated to dryness at 60° C. under reduced pressure (2.7 kPa)

Quellen und Nachweise

ORD-Eintrag
ord-4a4761a2e7524d8499e20dfd506b9662
Quelldatensatz
uspto-grants-2005_03
Patentnummer
US06872717B2

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