Water → Methyl 4-[(ethoxycarbonyl)phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate ethanedioate

HRID 1973846Notes

Reaction equation

HRID 1973846 reaction equation
Br[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:10]([O:12][C:13]([N:15]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:16]1([C:22]([O:24][CH3:25])=[O:23])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:14])[CH3:11].C(N(CC)CC)C.CN(C)C(=[O:43])C.[OH2:45]>>[C:22]([OH:24])(=[O:23])[C:16]([OH:43])=[O:45].[CH2:10]([O:12][C:13]([N:15]([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:16]1([C:22]([O:24][CH3:25])=[O:23])[CH2:21][CH2:20][N:19]([CH2:2][CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:18][CH2:17]1)=[O:14])[CH3:11]

Participants

6

Reactant 5

HCID 962WaterHCID 7666Phenethyl bromideHCID 8471TriethylamineHCID 31374DimethylacetamideHCID 54241043Methyl 4-[(ethoxycarbonyl)phenylamino]-4-piperidinecarboxylate

Product 1

HCID 86734319Methyl 4-[(ethoxycarbonyl)phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate ethanedioate

Conditions

Temperature
70 °C

Procedure

A mixture of 7.73 parts of (2-bromoethyl)benzene, 11.7 parts of methyl 4-[(ethoxycarbonyl)phenylamino]-4-piperidinecarboxylate, 6.9 parts of N,N-diethylethanamine and 171 parts of N,N-dimethylacetamide is stirred for 3 hours at 70° C. The reaction mixture is cooled to room temperature and poured onto 600 parts of water. The product is extracted with 360 parts of benzene. The extract is washed three times with water, dried, filtered and evaporated. The residue is purified twice by column-chromatography over silica gel using first trichloromethane and then a mixture of trichloromethane and methanol (95:5) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is converted into the ethanedioate salt in 2-propanol. The salt is filtered off and boiled in 2-propanol. The product is filtered off and dried in vacuo at 120° C, yielding 5 parts of methyl 4-[(ethoxycarbonyl)phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate ethanedioate; mp. 206.8° C.

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. extractionThe product is extracted with 360 parts of benzene
  3. washThe extract is washed three times with water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is purified twice by column-chromatography over silica gel using first trichloromethane
  8. additiona mixture of trichloromethane and methanol (95:5) as eluent
  9. customThe pure fractions are collected
  10. customthe eluent is evaporated
  11. filtrationThe salt is filtered off
  12. filtrationThe product is filtered off
  13. customdried in vacuo at 120° C

Sources & evidence

ORD record
ord-91623f5b0f674e70990fd9bc08bdb423
Source dataset
uspto-grants-1976_12
Patent number
US03998834

Reaction notes

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