Reaction #53512

Reaction equation

potassium carbonate

morpholine

1-benzhydryl-3-{[3-(4-bromobutoxy)phenyl]methanesulfonylmethylene}azetidine

→

4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)methanesulfonylmethyl]phenoxy}butyl)morpholine

Solvents

ethyl acetate

water

acetonitrile

Conditions

Workup

1. 1
   Otherclose to 20° C.
2. 2
   WashThe separated organic phase is washed with 4 cm3 of a saturated aqueous sodium chloride solution
3. 3
   Dryingdried over magnesium sulfate
4. 4
   Filtrationfiltered on sintered glass
5. 5
   Concentrationconcentrated to dryness under reduced pressure (1 kPa) at a temperature
6. 6
   Otherclose to 40° C
7. 7
   OtherThe residue obtained
8. 8
   Otheris purified by depositing, in solution in a minimum of dichloromethane, on chromatography on silica gel
9. 9
   Otherthe silica recovered
10. 10
    Washis washed on sintered glass with a dichloromethane-methanol mixture (80-20 by volume)
11. 11
    Concentrationconcentrated to dryness under reduced pressure (1 kPa) at a temperature
12. 12
    Otherclose to 40° C

Procedure

25 mg of potassium carbonate and then 0.016 cm3 of morpholine are successively added, at a temperature close to 20° C., under an inert atmosphere of argon, to a solution of 33 mg of 1-benzhydryl-3-{[3-(4-bromobutoxy)phenyl]methanesulfonylmethylene}azetidine in 2 cm3 of anhydrous acetonitrile. After stirring for 17 hours at a temperature close to 20° C., the reaction medium is diluted with 10 cm3 of ethyl acetate and 4 cm3 of water. The separated organic phase is washed with 4 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered on sintered glass and then concentrated to dryness under reduced pressure (1 kPa) at a temperature close to 40° C. The residue obtained is purified by depositing, in solution in a minimum of dichloromethane, on chromatography on silica gel deposited on a plate [(gel 0.5 mm thick, 2 plates of 20 20 cm, eluent: dichloromethane-methanol (92.5-7.5 by volume)]. The zone corresponding to the desired product adsorbed, located with UV rays, is scraped and the silica recovered is washed on sintered glass with a dichloromethane-methanol mixture (80-20 by volume). The filtrates are combined and concentrated to dryness under reduced pressure (1 kPa) at a temperature close to 40° C. 25.2 mg of 4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)methanesulfonylmethyl]phenoxy}butyl)morpholine are obtained in the form of a pale yellow foam [1H NMR spectrum (400 MHz, CDCl3, δ in ppm): 1.66 (mt, 2H), 1.81 (mt, 2H), 2.40 (t, J=7.5 Hz, 2H), 2.46 (mt, 4H), 2.77 (s, 3H), 3.72 (t, J=5 Hz, 4H), 3.84 (mt, 2H), 3.96 (t, J=6.5 Hz, 2H), 4.36 (mt, 2H), 4.53 (s, 1H), 6.87 (dd, J=8 and 2 Hz, 1H), 6.93 (d, J=8 Hz, 1H), 6.96 (d, J=2 Hz, 1H), from 7.10 to 7.35 (mt, 7H), 7.42 (d, J=8 Hz, 4H)].

Source