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

HRID 1017230

Reaktionsgleichung

Reaktionsgleichung von HRID 1017230
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 {fraction (60/40)} for fractions 18 to 27, and then {fraction (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. custom{fraction (60/40)} for fractions 18 to 27, and then {fraction (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-169c57e04b8146cb984c35e80a01f1a2
Quelldatensatz
uspto-grants-2002_11
Patentnummer
US06479479B2

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