Potassium Iodide → Alfentanil hydrochloride [USAN:USP]

HRID 1863034Notes

Reaction equation

HRID 1863034 reaction equation
[Cl:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])[N:7]([CH2:10][CH3:11])[N:6]=[N:5]1.[CH3:12][O:13][CH2:14][C:15]1([N:21]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:22](=[O:25])[CH2:23][CH3:24])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>O.CC(C)CC(=O)C>[OH2:9].[ClH:1].[CH2:10]([N:7]1[C:8](=[O:9])[N:4]([CH2:3][CH2:2][N:18]2[CH2:19][CH2:20][C:15]([N:21]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:22](=[O:25])[CH2:23][CH3:24])([CH2:14][O:13][CH3:12])[CH2:16][CH2:17]2)[N:5]=[N:6]1)[CH3:11]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 162172NoralfentanilHCID 30179061-(2-Chloroethyl)-4-ethyl-1,4-dihydro-5H-tetrazol-5-one

Product 1

HCID 64762Alfentanil hydrochloride [USAN:USP]Yield 33.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 1.8 parts of 1-(2-chloroethyl)-4-ethyl-1,4-dihydro-5H-tetrazol-5-one, 3.45 parts of N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide, 5 parts of sodium carbonate, 0.2 parts of potassium iodide and 240 parts of 4-methyl-2-pentanone is stirred and refluxed overnight with water-separator. The reaction mixture is poured onto water 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 (97:3 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is converted into the hydrochloride salt in 2-propanone. The salt is filtered off and crystallized from 2-propanone, yielding 1.5 parts (33.3%) of N-{1-[2-(4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-piperidinyl}-N-phenylpropanamide monohydrochloride monohydrate; mp. 140.8° C.

Workup

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

Sources & evidence

ORD record
ord-fe9e3537c32b4b31b34fc88ebfa633c5
Source dataset
uspto-grants-1979_09
Patent number
US04167574

Reaction notes

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