Potassium Iodide → N-{1-[2-(4,5-dihydro-4-methyl-5-oxo-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-piperidinyl}-N-phenylpropanamide ethanedioate

HRID 1863036Notes

Reaction equation

HRID 1863036 reaction equation
I[CH2:2][CH2:3][N:4]1[C:8](=[O:9])[N:7]([CH3:10])[N:6]=[N:5]1.[CH3:11][O:12][CH2:13][C:14]1([N:20]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:21](=[O:24])[CH2:22][CH3:23])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.[C:31](=O)([O-:33])[O-:32].[Na+].[Na+].[I-].[K+]>O.CC(C)CC(=O)C>[C:8]([OH:9])(=[O:12])[C:31]([OH:33])=[O:32].[CH3:10][N:7]1[C:8](=[O:9])[N:4]([CH2:3][CH2:2][N:17]2[CH2:18][CH2:19][C:14]([N:20]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:21](=[O:24])[CH2:22][CH3:23])([CH2:13][O:12][CH3:11])[CH2:15][CH2:16]2)[N:5]=[N:6]1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 162172NoralfentanilHCID 136767191,4-dihydro-1-(2-iodoethyl)-4-methyl-5H-tetrazol-5-one

Product 1

HCID 13676754N-{1-[2-(4,5-dihydro-4-methyl-5-oxo-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-piperidinyl}-N-phenylpropanamide ethanedioateYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 2.55 parts of 1,4-dihydro-1-(2-iodoethyl)-4-methyl-5H-tetrazol-5-one, 3.45 parts of N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide, 2 parts of sodium carbonate, 0.2 parts of potassium iodide and 160 parts of 4-methyl-2-pentanone is stirred and refluxed overnight with water-separator. The reaction mixture is cooled, 100 parts of water are added and the layers are separated. The aqueous phase is extracted with dichloromethane. The combined organic phases are dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (97:3 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is converted into the ethanedioate salt in 2-propanone. The salt is filtered off and crystallized from 2-propanone, yielding 2.1 parts (42%) of N-{1-[2-(4,5-dihydro-4-methyl-5-oxo-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-piperidinyl}-N-phenylpropanamide ethanedioate (1:1); mp. 155.9° C.

Workup

  1. temperatureThe reaction mixture is cooled
  2. customthe layers are separated
  3. extractionThe aqueous phase is extracted with dichloromethane
  4. customThe combined organic phases are dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is purified by column-chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (97:3 by volume) as eluent
  9. customThe pure fractions are collected
  10. customthe eluent is evaporated
  11. filtrationThe salt is filtered off
  12. customcrystallized from 2-propanone

Sources & evidence

ORD record
ord-8ee3f447175e46de814d7d339fb537dc
Source dataset
uspto-grants-1979_09
Patent number
US04167574

Reaction notes

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