Acetic Acid → HCID 21530364, compound

HRID 1657834Notes

Reaction equation

HRID 1657834 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][CH:15]=[CH:14][C:13]=2[F:18])=[O:11])[CH2:4]1)#[N:2].C(Cl)(Cl)[Cl:20].C(O)(=[O:25])C>Cl.O>[CH3:1][N:3]1[CH2:8][CH2:7][CH2:6][CH:5]([CH2:9][C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[O:11])[CH2:4]1.[ClH:20].[C:1]([N:3]1[CH2:8][CH2:7][CH2:6][CH:5]([CH2:9][C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[O:11])[CH2:4]1)(=[O:25])[NH2:2]

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 6212ChloroformHCID 21530358HCID 21530358, compound

Product 2

HCID 21530364HCID 21530364, compoundHCID 21530368HCID 21530368, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Procedure

1-Methyl-3-(2-fluorophenacyl)piperidine was prepared essentially as described in Example 5. The 1-cyano analog was prepared from the 1-methyl compound by the procedure of Example 20. The crude 1-cyano-3-(2-fluorophenacyl)piperidine, 66.4 g, was dissolved in a mixture of 470 ml of glacial acetic acid, 150 ml of concentrated hydrochloric acid, and 150 ml of water. The resulting solution, under nitrogen, was heated on a steam-bath for 17.5 hours. The reaction solution was worked up essentially as described in Example 21, except that an oil separated during the diethyl ether extraction. The oil and diethyl ether extracts were combined and diethyl ether was distilled. The residue was subjected to the hydrolysis procedure, except that the volume of glacial acetic acid was reduced to 400 ml and hydrolysis time was reduced to 15.75 hours. Work-up procedure was the same. During diethyl ether extraction, an oil again separated. The addition of chloroform to the multilayer mixture caused a precipitate to form in both the aqueous and chloroform layers. Solid also formed in the oil layer which remained insoluble. The solid in the chloroform layer was isolated by filtration and recrystallized three times from acetone/diethyl ether to give 1-carbamoyl-3-(2-fluorophenacyl)piperidine hydrochloride, mp 125°-128°. The following elemental analysis was obtained:

Workup

  1. temperatureThe resulting solution, under nitrogen, was heated on a steam-bath for 17.5 hours
  2. customseparated during the diethyl ether extraction
  3. distillationdiethyl ether was distilled
  4. customThe residue was subjected to the hydrolysis procedure, except that the volume of glacial acetic acid
  5. customwas reduced to 400 ml and hydrolysis time
  6. extractionDuring diethyl ether extraction
  7. customan oil again separated
  8. additionThe addition of chloroform to the multilayer mixture
  9. customto form in both the aqueous and chloroform layers
  10. customSolid also formed in the oil layer which
  11. customrecrystallized three times from acetone/diethyl ether

Sources & evidence

ORD record
ord-247ed4c884a740929d9c8725591d596f
Source dataset
uspto-grants-1976_06
Patent number
US03962257

Reaction notes

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