Water → HCID 86736639, compound

HRID 1863038Notes

Reaction equation

HRID 1863038 reaction equation
[CH2:1]([N:3]1[C:7](=[O:8])[N:6]([CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][C:14]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)([C:17]([O:19][CH3:20])=[O:18])[CH2:13][CH2:12]2)[N:5]=[N:4]1)[CH3:2].[CH:28]1([C:31](Cl)=[O:32])[CH2:30][CH2:29]1.C(N(CC)CC)C.CC1C=CC=CC=1.[OH2:48]>>[C:17]([OH:19])(=[O:18])[C:14]([OH:32])=[O:48].[CH:28]1([C:31]([N:21]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:14]2([C:17]([O:19][CH3:20])=[O:18])[CH2:13][CH2:12][N:11]([CH2:10][CH2:9][N:6]3[C:7](=[O:8])[N:3]([CH2:1][CH3:2])[N:4]=[N:5]3)[CH2:16][CH2:15]2)=[O:32])[CH2:30][CH2:29]1

Participants

6

Reactant 5

HCID 962WaterHCID 1140TolueneHCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 20393091HCID 20393091, compound

Product 1

HCID 86736639HCID 86736639, compoundYield 17.5%

Procedure

A mixture of 5.7 parts of methyl 1-[2-(4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-1-yl)ethyl]-4-(phenylamino)-4-piperidinecarboxylate, 1.9 parts of cyclopropanecarbonyl chloride, 2.7 parts of N,N-diethylethanamine and 68 parts of methylbenzene is stirred and refluxed overnight. The reaction mixture is cooled, 100 parts of water are added and the layers are separated. The organic phase is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions are collected and treated with 1 part of ethanedioic acid. The formed ethanedioate salt is filtered off and crystallized from a mixture of 2-propanone and 2,2'-oxybispropane, yielding 1.5 parts (17.5%) of methyl 4-[(cyclopropylcarbonyl)phenylamino]-1-[2-(4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-1-yl)ethyl]-4-piperidinecarboxylate ethanedioate (2:3); mp. 181.5° C.

Workup

  1. temperaturerefluxed overnight
  2. temperatureThe reaction mixture is cooled
  3. customthe layers are separated
  4. customThe organic phase is dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is purified by column-chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
  9. customThe pure fractions are collected
  10. additiontreated with 1 part of ethanedioic acid
  11. filtrationThe formed ethanedioate salt is filtered off
  12. customcrystallized from a mixture of 2-propanone and 2,2'-oxybispropane

Sources & evidence

ORD record
ord-0f307dcb0c5b4cb49f0e5cd7c7dbc3e6
Source dataset
uspto-grants-1979_09
Patent number
US04167574

Reaction notes

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