Hydrochloric Acid → 4-[4,4-bis(4-fluorophenyl)butyl]-N-(2-hydroxyethyl)-2-piperazinecarboxamide

HRID 35330Notes

Reaction equation

HRID 35330 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[CH2:9][CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][N:15]3C(C)(C)[N:19]([CH2:22][CH2:23][OH:24])[C:20](=[O:21])[CH:14]3[CH2:13]2)=[CH:4][CH:3]=1.Cl>O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:27]2[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=2)[CH2:9][CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][NH:15][CH:14]([C:20]([NH:19][CH2:22][CH2:23][OH:24])=[O:21])[CH2:13]2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 212956477-[4,4-bis(4-fluorophenyl)butyl]hexahydro-2-(2-hydroxyethyl)-3,3-dimethylimidazo[1,5-a]pyrazin-1(5H)-one

Product 1

HCID 212956904-[4,4-bis(4-fluorophenyl)butyl]-N-(2-hydroxyethyl)-2-piperazinecarboxamideYield 100%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 40 parts of 7-[4,4-bis(4-fluorophenyl)butyl]hexahydro-2-(2-hydroxyethyl)-3,3-dimethylimidazo[1,5-a]pyrazin-1(5H)-one, 19 parts of hydrochloric acid solution 10.5N and 400 parts of water was stirred for one hour in a boiling water-bath on a Rotavapor. After cooling, the reaction mixture was washed twice with 140 parts of 1,1'-oxybisethane. The aqueous phase was alkalized with ammonium hydroxide. The product was extracted twice with 140 parts of 1,1'-oxybisethane. The combined extracts were dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using first a mixture of trichloromethane and methanol (90:10 by volume) and then a mixture of trichloromethane and methanol saturated with ammonia (90:10 by volume) as eluents. The pure fractions were collected and the eluent was evaporated, yielding 33.7 parts (100%) of 4-[4,4-bis(4-fluorophenyl)butyl]-N-(2-hydroxyethyl)-2-piperazinecarboxamide (intermediate 95).

Workup

  1. temperatureAfter cooling
  2. washthe reaction mixture was washed twice with 140 parts of 1,1'-oxybisethane
  3. extractionThe product was extracted twice with 140 parts of 1,1'-oxybisethane
  4. customThe combined extracts were dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column-chromatography over silica gel using first
  8. additiona mixture of trichloromethane and methanol (90:10 by volume)
  9. additiona mixture of trichloromethane and methanol saturated with ammonia (90:10 by volume) as eluents
  10. customThe pure fractions were collected
  11. customthe eluent was evaporated

Sources & evidence

ORD record
ord-59b6a0da634944dc812997da1485cb39
Source dataset
uspto-grants-1988_08
Patent number
US04766125

Reaction notes

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