2-Morpholinoethylamine → N-(2-morpholinoethyl)-1-[1-(4-chlorophenyl)cyclobutyl]-2-methoxyethylamine dihydrochloride

HRID 728294Notes

Reaction equation

HRID 728294 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][NH2:9])[CH2:3][CH2:2]1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2([C:21](=O)[CH2:22][O:23][CH3:24])[CH2:20][CH2:19][CH2:18]2)=[CH:13][CH:12]=1.[BH4-].[Na+]>CC(O)C>[ClH:10].[ClH:10].[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][NH:9][CH:21]([C:17]2([C:14]3[CH:15]=[CH:16][C:11]([Cl:10])=[CH:12][CH:13]=3)[CH2:18][CH2:19][CH2:20]2)[CH2:22][O:23][CH3:24])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 4082852-MorpholinoethylamineHCID 4311764Sodium borohydrideHCID 198236811-[1-(4-Chlorophenyl)cyclobutyl]-2-methoxyethanone

Product 1

HCID 67945593N-(2-morpholinoethyl)-1-[1-(4-chlorophenyl)cyclobutyl]-2-methoxyethylamine dihydrochloride

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

2-(Morpholino)ethylamine (20 g) was heated at 175°-180° C. and 1-(4-chlorophenyl)cyclobutyl-2-methoxyethanone (20 g) prepared as described in Example 206 was added dropwise with stirring over 1 hour. The mixture was stirred at 180° C. for a further hour. A stream of nitrogen was passed through the reaction mixture to remove any water formed. The mixture was cooled and added dropwise to a suspension of sodium borohydride (10 g) in propan-2-ol (800 ml). The mixture was then heated under reflux for 3 hours. Propan-2-ol was evaporated and an ice/water mixture was added to the residue which was cooled and acidified with 5N hydrochloric acid. The acidified mixture was basified and extracted with ether Hydrogen chloride gas was passed into the dried extract which was then evaporated to dryness. The residue was heated with propan-2-ol, filtered and the filtrate evaporated to dryness. The residue was partitioned between ether and 2N hydrochloric acid. The acid layer was washed with ether, basified and extracted with ether. Hydrogen chloride gas was passed into the ether extract which was then evaporated to dryness to give a residue which was recrystallised from propan-2-ol to give N-(2-morpholinoethyl)-1-[1-(4-chlorophenyl)cyclobutyl]-2-methoxyethylamine dihydrochloride (m.p. 234°-237° C.).

Workup

  1. additionwas added dropwise
  2. stirringThe mixture was stirred at 180° C. for a further hour
  3. customto remove any water
  4. customformed
  5. temperatureThe mixture was cooled
  6. temperatureThe mixture was then heated
  7. temperatureunder reflux for 3 hours
  8. customPropan-2-ol was evaporated
  9. additionan ice/water mixture was added to the residue which
  10. temperaturewas cooled
  11. extractionextracted with ether Hydrogen chloride gas
  12. extractionextract which
  13. customwas then evaporated to dryness
  14. temperatureThe residue was heated with propan-2-ol
  15. filtrationfiltered
  16. customthe filtrate evaporated to dryness
  17. customThe residue was partitioned between ether and 2N hydrochloric acid
  18. washThe acid layer was washed with ether
  19. extractionextracted with ether
  20. extractionextract which
  21. customwas then evaporated to dryness
  22. customto give a residue which
  23. customwas recrystallised from propan-2-ol

Sources & evidence

ORD record
ord-1dbc8f2edaca413fb1375de784a5b9f4
Source dataset
uspto-grants-1991_09
Patent number
US05047432

Reaction notes

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