Acetic Acid → 1-Carbamoyl-3-(4-fluorophenacyl)piperidine

HRID 1657832Notes

Reaction equation

HRID 1657832 reaction equation
[C:1]([N:3]1[CH2:8][CH2:7][CH2:6][CH:5]([CH2:9][C:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[O:11])[CH2:4]1)#[N:2].C(O)(=[O:21])C>Cl.O>[C:1]([N:3]1[CH2:8][CH2:7][CH2:6][CH:5]([CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=2)=[O:11])[CH2:4]1)(=[O:21])[NH2:2]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 215303571-Cyano-3-(4-fluorophenacyl)piperidine

Product 1

HCID 215303701-Carbamoyl-3-(4-fluorophenacyl)piperidine

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Procedure

1-Cyano-3-(4-fluorophenacyl)piperidine (Example 19), 21.5 g, was dissolved in a mixture of 150 ml of glacial acetic acid, 30 ml of concentrated aqueous hydrochloric acid, and 70 ml of water. The resulting solution, under a nitrogen atmosphere, was heated on a steam-bath for 16 hours. The reaction solution was distilled under reduced pressure, the residue was diluted with water, and the resulting solution was made alkaline with 3 N sodium hydroxide. Upon extracting the alkaline aqueous solution with ethyl ether, solid precipitated and was isolated by filtration and washed with ether. The solid, 6.7 g, was recrystallized once from aqueous acetone and then four times from acetone/diethyl ether, to give 1-carbamoyl-3-(4-fluorophenacyl)piperidine, mp 136°-137.5°. The following elemental analysis was obtained:

Workup

  1. temperatureThe resulting solution, under a nitrogen atmosphere, was heated on a steam-bath for 16 hours
  2. distillationThe reaction solution was distilled under reduced pressure
  3. additionthe residue was diluted with water
  4. extractionUpon extracting the alkaline aqueous solution with ethyl ether, solid
  5. customprecipitated
  6. customwas isolated by filtration
  7. washwashed with ether
  8. customThe solid, 6.7 g, was recrystallized once from aqueous acetone

Sources & evidence

ORD record
ord-d6a55369769a4cc0bede3e3e6cc97334
Source dataset
uspto-grants-1976_06
Patent number
US03962257

Reaction notes

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