Water → HCID 12298161, compound

HRID 1448304Notes

Reaction equation

HRID 1448304 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2([C:22]([OH:24])=[O:23])[CH2:14][CH2:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[H-].[Na+].IC.[OH2:29].[CH3:30]N(C)P(=[O:39])(N(C)C)N(C)C>>[C:22]([OH:24])(=[O:23])[C:9]([OH:39])=[O:29].[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2([C:22]([O:24][CH3:30])=[O:23])[CH2:14][CH2:13][N:12]([CH2:15][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH2:11][CH2:10]2)=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 962WaterHCID 6328Methyl iodideHCID 12679HexamethylphosphoramideHCID 24758Sodium hydrideHCID 122981414-Piperidinecarboxylic acid, 4-[(4-fluorophenyl)amino]-1-(phenylmethyl)-

Product 1

HCID 12298161HCID 12298161, compound

Procedure

70 Parts of 4-[(4-fluorophenyl)amino]-1-(phenylmethyl)-4-piperidinecarboxylic acid are dissolved in 450 parts of dry hexamethylphosphoric triamide at 120° C. This solution is cooled to room temperature and 6 parts of sodium hydride dispersion 78% are added portionwise at a temperature below 30° C. After stirring for 1.50 hours at room temperature, there are added dropwise 32.5 parts of iodomethane at a temperature below 15° C. Upon completion, stirring is continued for 28 hours at room temperature. The reaction mixture is poured onto 800 parts of water and the product is extracted with methylbenzene. The extract is washed successively with water, a 10% sodium hydroxide solution and again twice with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 5% 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 and crystallized from 2-propanol, yielding methyl 4-[(4-fluorophenyl)amino]-1-(phenylmethyl)-4-piperidinecarboxylate ethanedioate; mp. 168.6° C.

Workup

  1. stirringUpon completion, stirring
  2. waitis continued for 28 hours at room temperature
  3. extractionthe product is extracted with methylbenzene
  4. washThe extract is washed successively with water
  5. dry with materiala 10% sodium hydroxide solution and again twice with water, dried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue is purified by column-chromatography over silica gel using
  9. additiona mixture of trichloromethane and 5% of methanol as eluent
  10. customThe pure fractions are collected
  11. customthe eluent is evaporated
  12. filtrationThe salt is filtered off
  13. customcrystallized from 2-propanol

Sources & evidence

ORD record
ord-c2713b7c7ac74e6894d0d2831cb45033
Source dataset
uspto-grants-1979_12
Patent number
US04179569

Reaction notes

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