Water → HCID 86734313, compound

HRID 1448335Notes

Reaction equation

HRID 1448335 reaction equation
IC.[O:3](CC)[CH2:4]C.[Li].[CH3:9][O:10][C:11]1[CH:12]=[C:13]([NH:17][C:18]2([C:32]([OH:34])=[O:33])[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:20][CH2:19]2)[CH:14]=[CH:15][CH:16]=1.[OH2:35]>>[C:32]([OH:34])(=[O:33])[C:18]([OH:3])=[O:35].[CH3:9][O:10][C:11]1[CH:12]=[C:13]([NH:17][C:18]2([C:32](=[O:33])[CH3:4])[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:20][CH2:19]2)[CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 5

HCID 962WaterHCID 3283Diethyl Ether3×HCID 6328Methyl iodideHCID 3028194LithiumHCID 20382243HCID 20382243, compound

Product 1

HCID 86734313HCID 86734313, compoundYield 96.5%

Procedure

To start the reaction, a small amount of a solution of 101.4 parts of iodomethane in 81 parts of dry 1,1'-oxybisethane is dropped to a stirred solution of 8.95 parts of lithium in 81 parts of dry 1,1'-oxybisethane. After the addition of 244 parts of dry 1,1'-oxybisethane, the remainder of the solution is added dropwise at reflux temperature. Stirring at reflux is continued for one hour. Then there are added portionwise 23 parts of 4-[(3-methoxyphenyl)amino]-1-(2-phenylethyl)-4-piperidinecarboxylic acid (a violent reaction occurs whereby reflux temperature is maintained). Upon completion, stirring at reflux is continued for one hour. The reaction mixture is decomposed by the dropwise addition (carefully) of water. The organic phase is separated, washed with water, dried, filtered and evaporated. The oily residue is purified twice by column-chromatography over silica gel using first a mixture of trichloromethane and 6% of methanol and then a mixture of trichloromethane and 4% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue is converted into the ethanedioate salt in 2-propanol. The salt is filtered off, dried and crystallized twice from methanol, yielding 3.08 parts (96.5%) of 1-{4-[(3-methoxyphenyl)amino]-1-(2-phenylethyl)-4-piperidinyl}ethanone ethanedioate; mp. 188° C.

Workup

  1. customthe reaction
  2. additionthe remainder of the solution is added dropwise
  3. temperatureat reflux temperature
  4. temperatureat reflux
  5. customa violent reaction
  6. temperaturereflux temperature
  7. temperatureis maintained)
  8. stirringUpon completion, stirring
  9. temperatureat reflux
  10. waitis continued for one hour
  11. customThe organic phase is separated
  12. washwashed with water
  13. customdried
  14. filtrationfiltered
  15. customevaporated
  16. customThe oily residue is purified twice by column-chromatography over silica gel using first
  17. additiona mixture of trichloromethane and 6% of methanol
  18. additiona mixture of trichloromethane and 4% of methanol as eluent
  19. customThe pure fractions are collected
  20. customthe eluent is evaporated
  21. filtrationThe salt is filtered off
  22. customdried
  23. customcrystallized twice from methanol

Sources & evidence

ORD record
ord-f978b2eae0ac49c78539ec820e83bb04
Source dataset
uspto-grants-1979_12
Patent number
US04179569

Reaction notes

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