Reaktion #46347

Reaktionsgleichung

1-benzhydrylazetidin-3-one

azetidine

n-butyllithium

3,5-difluorobenzyl methyl sulfone

acetyl chloride

→

3-acetoxy-1-benzhydryl-3-[(3,5-difluorophenyl)(methyl-sulfonyl)methyl]azetidine

Lösungsmittel

dichloromethane

dichloromethane

water

hexane

tetrahydrofuran

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigebe prepared in the following manner
2. 2
   workup.STIRRINGThe reaction mixture is stirred for 1.5 hours at a temperature in the region of −30° C.
3. 3
   workup.WAITto return to a temperature in the region of −10° C. over about 30 minutes
4. 4
   workup.STIRRINGAfter stirring vigorously for 30 minutes
5. 5
   Waschendecantation, the organic phase is washed with 3 times 150 cm3 of a saturated aqueous sodium hydrogen carbonate solution, 150 cm3 of a saturated aqueous sodium chloride solution
6. 6
   Trocknendried over magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated to dryness under reduced pressure
9. 9
   SonstigeThe crystalline residue obtained
10. 10
    SonstigeThe white suspension obtained
11. 11
    workup.WAITto stand overnight at a temperature in the region of 20° C.
12. 12
    Sonstigethe solid obtained
13. 13
    Waschenrinsed with diisopropyl ether
14. 14
    Sonstigedried under reduced pressure at a temperature in the region of 50° C

Vorschrift

3-Acetoxy-1-benzhydryl-3-[(3,5-difluoro-phenyl)methylsulfonyl)methyl]azetidine may be prepared may be prepared in the following manner: 47.1 cm3 of 1.6 N n-butyllithium in solution in hexane are added dropwise over approximately 25 minutes to a suspension of 12.37 g of 3,5-difluorobenzyl methyl sulfone in 200 cm3 of tetrahydrofuran, under an inert nitrogen atmosphere at a temperature in the region of −30° C. The cloudy yellow solution is stirred at a temperature in the region of −30° C. for 2 hours and then a solution of 11.87 g of 1-benzhydrylazetidin-3-one in 75 cm3 of dichloromethane is added dropwise. The reaction mixture is stirred for 1.5 hours at a temperature in the region of −30° C. and then 6.07 cm3 of acetyl chloride are added and the temperature of the medium is allowed to return to a temperature in the region of −10° C. over about 30 minutes. 200 cm3 of water and 100 cm3 of dichloromethane are added. After stirring vigorously for 30 minutes and decantation, the organic phase is washed with 3 times 150 cm3 of a saturated aqueous sodium hydrogen carbonate solution, 150 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The crystalline residue obtained is taken up in 50 cm3 of boiling ethanol. The white suspension obtained is allowed to stand overnight at a temperature in the region of 20° C. and then the solid obtained is drained over sintered glass, rinsed with diisopropyl ether and dried under reduced pressure at a temperature in the region of 50° C. 19.5 g of 3-acetoxy-1-benzhydryl-3-[(3,5-difluorophenyl)(methyl-sulfonyl)methyl]azetidine are thus obtained in the form of white crystals.

Quelle