Formic Acid → N-methyl-N-(2-morpholinoethyl)-1-[1-(4-chlorophenyl)cyclobutyl]-2-methoxyethylamine

HRID 728295Notes

Reaction equation

HRID 728295 reaction equation
Cl.Cl.[O:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][NH:11][CH:12]([C:16]2([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[CH2:19][CH2:18][CH2:17]2)[CH2:13][O:14][CH3:15])[CH2:5][CH2:4]1.[CH:27](O)=O.C=O>C(OCC)(=O)C>[CH3:27][N:11]([CH:12]([C:16]1([C:20]2[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=2)[CH2:17][CH2:18][CH2:19]1)[CH2:13][O:14][CH3:15])[CH2:10][CH2:9][N:6]1[CH2:5][CH2:4][O:3][CH2:8][CH2:7]1

Participants

5

Reactant 3

HCID 284Formic AcidHCID 712FormaldehydeHCID 67945593N-(2-morpholinoethyl)-1-[1-(4-chlorophenyl)cyclobutyl]-2-methoxyethylamine dihydrochloride

Product 1

HCID 19823697N-methyl-N-(2-morpholinoethyl)-1-[1-(4-chlorophenyl)cyclobutyl]-2-methoxyethylamine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of the product of Example 208 in the form of its free base (2.0 g), 98% formic acid (8 ml) and 37-40% aqueous formaldehyde solution (25 ml) was stirred at room temperature for 2 hours. The mixture was then heated at 95°-100° C. for 18 hours, cooled, basified and extracted with ether. The extract was washed with water and dried. Dry hydrogen chloride gas was passed into the ethereal solution. Evaporation of the solvent gave a residue which was heated with ethyl acetate (20 ml) to give a white solid which was partitioned between ether and water. The aqueous phase was basified and then extracted with ether. The extract was dried and evaporated to give a residue which was distilled using a Buchi Kugelrohr apparatus (200° C./0.5 mm) to give N-methyl-N-(2-morpholinoethyl)-1-[1-(4-chlorophenyl)cyclobutyl]-2-methoxyethylamine.

Workup

  1. temperatureThe mixture was then heated at 95°-100° C. for 18 hours
  2. temperaturecooled
  3. extractionextracted with ether
  4. washThe extract was washed with water
  5. customdried
  6. customEvaporation of the solvent
  7. customgave a residue which
  8. customto give a white solid which
  9. customwas partitioned between ether and water
  10. extractionextracted with ether
  11. customThe extract was dried
  12. customevaporated
  13. customto give a residue which
  14. distillationwas distilled
  15. customa Buchi Kugelrohr apparatus (200° C./0.5 mm)

Sources & evidence

ORD record
ord-8233a263b99e4973b3e03f691b66c5ba
Source dataset
uspto-grants-1991_09
Patent number
US05047432

Reaction notes

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