Reaktion #46335

Reaktionsgleichung

sodium hydrogen carbonate

methyl (+)-4-[(R*)-amino-(4-chlorophenyl)methyl]benzoate

epibromohydrin

→

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

Lösungsmittel

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstige1-{(R*)-(4-Chlorophenyl)[4-methoxycarbonyl)-phenyl]methyl}azetidin-3-ol, A isomer form, may be prepared
2. 2
   Einengenthe reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa)
3. 3
   SonstigeThe residue is chromatographed on a silica gel column (particle size 0.06-0.200 mm, diameter 3 cm, height 35 cm)
4. 4
   Wascheneluting under an argon pressure of 0.5 bar
5. 5
   workup.ADDITIONwith a mixture of cyclohexane and ethyl acetate (70/30 by volume for fractions 6 to 10
6. 6
   Sonstige60/40 for fractions 18 to 27, and then 50/50) and collecting 60-cm3 fractions
7. 7
   Einengenconcentrated to dryness under reduced pressure (2.7 kPa)
8. 8
   workup.STIRRINGAfter stirring for 48 hours at 20° C.
9. 9
   Filtration24 hours at 35° C., the mixture is filtered
10. 10
    Einengenthe filtrate is concentrated to dryness at 60° C. under reduced pressure (2.7 kPa)

Vorschrift

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.

Quelle