反应详情

温度

60 °C

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.

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)