Triethylamine → 1-(4,4'-Difluorobenzhydryl)-4-(5-(2,4-dimethoxyphenyl)-2,4-pentadienoyl)piperazine

HRID 414487Notes

Reaction equation

HRID 414487 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH:11]=[CH:12][CH:13]=[CH:14][C:15]([OH:17])=O.C(N(CC)CC)C.C(C(Cl)=O)C.[F:30][C:31]1[CH:50]=[CH:49][C:34]([CH:35]([N:43]2[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)[C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)=[CH:33][CH:32]=1>ClCCl.C(OCC)(=O)C.CCCCCC.O>[F:30][C:31]1[CH:50]=[CH:49][C:34]([CH:35]([N:43]2[CH2:44][CH2:45][N:46]([C:15](=[O:17])[CH:14]=[CH:13][CH:12]=[CH:11][C:4]3[CH:5]=[CH:6][C:7]([O:9][CH3:10])=[CH:8][C:3]=3[O:2][CH3:1])[CH2:47][CH2:48]2)[C:36]2[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=2)=[CH:33][CH:32]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 62324Propionyl chlorideHCID 1529321-(Bis(4-fluorophenyl)methyl)piperazineHCID 539851515-(2,4-Dimethoxyphenyl)-2,4-pentadienoic acid

Product 1

HCID 542344241-(4,4'-Difluorobenzhydryl)-4-(5-(2,4-dimethoxyphenyl)-2,4-pentadienoyl)piperazineYield 73.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
0 °C

Procedure

To 7.50 g (32.0 mmol) of 5-(2,4-dimethoxyphenyl)-2,4-pentadienoic acid were added 300 ml of dry dichloromethane and 4.46 ml (32.0 mmol) of triethylamine in the atmosphere of argon. The mixture was stirred at 0° C. followed by addition of 3.06 ml (32.0 mmol) of ethylcarbonyl chloride. The resulting mixture was stirred for 1 hour followed by addition of 11.04 g (38.4 mmol) of 4,4'-difluorobenzhydrylpiperazine in 50 ml of dry dichloromethane. Temperature of the mixture was raised to room temperature followed by stirring for additional 16 hours. After addition of water, the mixture was extracted with dichloromethane. The organic layer was washed successively with aqueous 1N-hydrochloric acid solution, a saturated aqueous solution of sodium chloride and a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. There was obtained a residue, which was subjected to column chromatography on silica gel to give 11.9 g (23.6 mmol) of 1-(4,4'-difluorobenzhydryl)-4-(5-(2,4-dimethoxyphenyl)-2,4-pentadienoyl)piperazine from eluate of ethyl acetate-hexane (1:1).

Workup

  1. stirringThe resulting mixture was stirred for 1 hour
  2. temperatureTemperature of the mixture was raised to room temperature
  3. stirringby stirring for additional 16 hours
  4. extractionthe mixture was extracted with dichloromethane
  5. washThe organic layer was washed successively with aqueous 1N-hydrochloric acid solution
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThere was obtained a residue, which

Sources & evidence

ORD record
ord-b72fce11a4b04075aadeccfa623e76d4
Source dataset
uspto-grants-1988_12
Patent number
US04792553

Reaction notes

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