Methyl iodide → HCID 12298162, compound

HRID 1448312Notes

Reaction equation

HRID 1448312 reaction equation
[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][C:11]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)([C:14]([OH:16])=[O:15])[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:28]N(C)P(=O)(N(C)C)N(C)C.[H-].[Na+].IC>CC1C=CC=CC=1>[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][C:11]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:25])[F:26])[CH:19]=3)([C:14]([O:16][CH3:28])=[O:15])[CH2:10][CH2:9]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 12679HexamethylphosphoramideHCID 24758Sodium hydrideHCID 12298142HCID 12298142, compound

Product 1

HCID 12298162HCID 12298162, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of 78 parts of 1-(phenylmethyl)-4-[3-(trifluoromethyl)phenylamino]-4-piperidinecarboxylic acid in 470 parts of dry hexamethylphosphoric triamide are added portionwise 6.3 parts of sodium hydride dispersion 78% (slightly exothermic reaction). After stirring for one hour at room temperature, 29.3 parts of iodomethane are added dropwise. Upon completion, stirring is continued overnight at room temperature. Methylbenzene is added and the whole is washed with water. The organic phase is separated, washed with a sodium hydroxide solution 10% and with water, dried, filtered and evaporated. The oily residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 3% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue is converted into the hydrochloride salt in 1,1'-oxybisethane and 2-propanol. After stirring vigorously, the salt is filtered off and crystallized twice from 4-methyl-2-pentanone, yielding methyl 1-(phenylmethyl)-4-[3-(trifluoromethyl)phenylamino]-4-piperidinecarboxylate; mp. 120.4° C.

Workup

  1. customslightly exothermic reaction)
  2. stirringUpon completion, stirring
  3. waitis continued overnight at room temperature
  4. washthe whole is washed with water
  5. customThe organic phase is separated
  6. washwashed with a sodium hydroxide solution 10% and with water
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. customThe oily residue is purified by column-chromatography over silica gel using
  11. additiona mixture of trichloromethane and 3% of methanol as eluent
  12. customThe pure fractions are collected
  13. customthe eluent is evaporated
  14. stirringAfter stirring vigorously
  15. filtrationthe salt is filtered off
  16. customcrystallized twice from 4-methyl-2-pentanone

Sources & evidence

ORD record
ord-e5d330a604d8419486a7373006ea4374
Source dataset
uspto-grants-1979_12
Patent number
US04179569

Reaction notes

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