Morpholine → 4-(4-{3-[(1-Benzhydrylazetidin-3-ylidene)methanesulfonylmethyl]phenoxy}butyl)morpholine

HRID 1058841Notes

Reaction equation

HRID 1058841 reaction equation
C(=O)([O-])[O-].[K+].[K+].[NH:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.[CH:13]([N:26]1[CH2:29][C:28](=[CH:30][S:31]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([O:41][CH2:42][CH2:43][CH2:44][CH2:45]Br)[CH:36]=2)(=[O:33])=[O:32])[CH2:27]1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(#N)C.C(OCC)(=O)C.O>[CH:13]([N:26]1[CH2:29][C:28](=[CH:30][S:31]([CH2:34][C:35]2[CH:36]=[C:37]([CH:38]=[CH:39][CH:40]=2)[O:41][CH2:42][CH2:43][CH2:44][CH2:45][N:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)(=[O:33])=[O:32])[CH2:27]1)([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 225652911-Benzhydryl-3-{[3-(4-bromobutoxy)phenyl]methanesulfonylmethylene}azetidine

Product 1

HCID 696357434-(4-{3-[(1-Benzhydrylazetidin-3-ylidene)methanesulfonylmethyl]phenoxy}butyl)morpholine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

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)].

Workup

  1. customclose to 20° C.
  2. washThe separated organic phase is washed with 4 cm3 of a saturated aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered on sintered glass
  5. concentrationconcentrated to dryness under reduced pressure (1 kPa) at a temperature
  6. customclose to 40° C
  7. customThe residue obtained
  8. customis purified by depositing, in solution in a minimum of dichloromethane, on chromatography on silica gel
  9. customthe silica recovered
  10. washis washed on sintered glass with a dichloromethane-methanol mixture (80-20 by volume)
  11. concentrationconcentrated to dryness under reduced pressure (1 kPa) at a temperature
  12. customclose to 40° C

Sources & evidence

ORD record
ord-6249990d223c43e0971b0132f7598b5d
Source dataset
uspto-grants-2003_02
Patent number
US06518264B2

Reaction notes

Loading…