1,4-Dioxane hydrochloride → HCID 136348250, compound

HRID 1691770Notes

Reaction equation

HRID 1691770 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:12][C:11](=[O:13])[O:10][N:9]=2)[CH:5]=[C:4]([F:14])[C:3]=1[N:15]1[CH2:20][CH2:19][CH:18]([CH2:21][N:22]([C@@H:30]([C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH:35]=[CH:34][CH:33]=2)[CH3:31])C(=O)OC(C)(C)C)[CH:17]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH2:16]1.[ClH:48].O1CCOCC1>>[ClH:48].[F:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:12][C:11](=[O:13])[O:10][N:9]=2)[CH:5]=[C:4]([F:14])[C:3]=1[N:15]1[CH2:20][CH2:19][CH:18]([CH2:21][NH:22][C@@H:30]([C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH:35]=[CH:34][CH:33]=2)[CH3:31])[CH:17]([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:16]1

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 136348244HCID 136348244, compound

Product 1

HCID 136348250HCID 136348250, compound

Procedure

To 183 mg of tert-butyl ({1-[2,6-difluoro-4-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl]-3-phenylpiperidin-4-yl}methyl)[(1R)-1-(1-naphthyl)ethyl]carbamate was added 1.5 mL of a 4 M hydrogen chloride/1,4-dioxane solution. After stirring at room temperature for 2 hours, the reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol), followed by addition of 0.5 mL of a 4 M hydrogen chloride/1,4-dioxane solution, and further concentration under reduced pressure. To the obtained residue were added ethanol and ethyl acetate, followed by heating under reflux, and then being left to be cooled to room temperature. The precipitate was collected by filtration, and dried under reduced pressure, and isopropanol and ethyl acetate were added thereto, followed by heating under reflux, and then being left to be cooled to room temperature. The precipitate was collected by filtration, and dried under reduced pressure to obtain 57 mg of 3-{3,5-difluoro-4-[4-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]phenyl}-1,2,4-oxadiazol-5(4H)-one hydrochloride as a white solid.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by silica gel column chromatography (chloroform/methanol)
  3. additionfollowed by addition of 0.5 mL of a 4 M hydrogen chloride/1,4-dioxane solution, and further concentration under reduced pressure
  4. additionTo the obtained residue were added ethanol and ethyl acetate
  5. temperatureby heating
  6. temperatureunder reflux
  7. waitbeing left
  8. temperatureto be cooled to room temperature
  9. filtrationThe precipitate was collected by filtration
  10. dry with materialdried under reduced pressure, and isopropanol and ethyl acetate
  11. additionwere added
  12. temperatureby heating
  13. temperatureunder reflux
  14. waitbeing left
  15. temperatureto be cooled to room temperature
  16. filtrationThe precipitate was collected by filtration
  17. customdried under reduced pressure

Sources & evidence

ORD record
ord-24974b7727274e02b421f99f7c1f36a8
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

Loading…