Diethyl Ether → 1-[4-(4-Methylanilino)-1-(2-phenylethyl)piperidin-4-yl]ethan-1-one

HRID 1973833Notes

Reaction equation

HRID 1973833 reaction equation
[Li].[O:2]([CH2:5][CH3:6])CC.IC.[CH3:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2(C(O)=O)[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:19][CH2:18]2)=[CH:12][CH:11]=1>O>[CH3:9][C:10]1[CH:11]=[CH:12][C:13]([NH:16][C:17]2([C:5](=[O:2])[CH3:6])[CH2:18][CH2:19][N:20]([CH2:23][CH2:24][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH2:21][CH2:22]2)=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 3283Diethyl Ether3×HCID 6328Methyl iodideHCID 3028194LithiumHCID 20382290HCID 20382290, compound

Product 1

HCID 203823741-[4-(4-Methylanilino)-1-(2-phenylethyl)piperidin-4-yl]ethan-1-oneYield 62.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of 17.4 parts of lithium in 140 parts of dry 1,1'-oxybisethane is added dropwise a small amount of a solution of 193.7 parts of iodomethane in 210 parts of dry 1,1'-oxybisethane. After the reaction is started by heating, there are added 420 parts of dry 1,1'-oxybisethane. The remainder of the solution is added dropwise at reflux temperature. Stirring at reflux is continued for 45 minutes. Then there are added portionwise (quickly) 41.8 parts of 4-[(4-methylphenyl)amino]-1-(2-phenylethyl)-4-piperidinecarboxylic acid (exothermic reaction: reflux temperature is maintained). Upon completion, stirring at reflux is continued for 1 hour. The reaction mixture is cooled in an ice-bath and decomposed by the dropwise addition of 1000 parts of water. The organic layer is separated and discarded. The aqueous phase is extracted with 1,1'-oxybisethane. The extract is dried, filtered and evaporated. The solid residue is crystallized from 2,2'-oxybispropane. The product is filtered off and recrystallized from 2,2' -oxybispropane, yielding 26 parts (62.4%) of 1-{4-[(4-methylphenyl)amino]-1-(2-phenylethyl)-4-piperidinyl} ethanone; mp. 133.7° C.

Workup

  1. temperatureby heating
  2. additionThe remainder of the solution is added dropwise
  3. temperatureat reflux temperature
  4. temperatureat reflux
  5. stirringUpon completion, stirring
  6. temperatureat reflux
  7. waitis continued for 1 hour
  8. temperatureThe reaction mixture is cooled in an ice-bath
  9. customThe organic layer is separated
  10. extractionThe aqueous phase is extracted with 1,1'-oxybisethane
  11. customThe extract is dried
  12. filtrationfiltered
  13. customevaporated
  14. customThe solid residue is crystallized from 2,2'-oxybispropane
  15. filtrationThe product is filtered off
  16. customrecrystallized from 2,2' -oxybispropane

Sources & evidence

ORD record
ord-fcc05120d9124eb4a0b304fbb2924acf
Source dataset
uspto-grants-1976_12
Patent number
US03998834

Reaction notes

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