Hydrochloric Acid → 8-(4-trifluoromethyl-1-piperazinyl)-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid

HRID 1649455Notes

Reaction equation

HRID 1649455 reaction equation
C1(C)C=CC(S(O[C:11]2[C:22]3=[C:23]4[N:18]([CH2:19][CH2:20][CH2:21]3)[CH:17]=[C:16]([C:24]([OH:26])=[O:25])[C:15](=[O:27])[C:14]4=[CH:13][CH:12]=2)(=O)=O)=CC=1.[F:29][C:30]([F:38])([F:37])[N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.CS(C)=O.Cl>O>[F:29][C:30]([F:38])([F:37])[N:31]1[CH2:36][CH2:35][N:34]([C:11]2[C:22]3=[C:23]4[N:18]([CH2:19][CH2:20][CH2:21]3)[CH:17]=[C:16]([C:24]([OH:26])=[O:25])[C:15](=[O:27])[C:14]4=[CH:13][CH:12]=2)[CH2:33][CH2:32]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 128996818-(p-toluenesulfonyloxy)-6,7-dihydro-1-oxo-1H,5H-benzo-[ij]quinolizine-2-carboxylic acidHCID 227170471-(Trifluoromethyl)piperazine

Product 1

HCID 132695168-(4-trifluoromethyl-1-piperazinyl)-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acidYield 52.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 3.4 g of 8-(p-toluenesulfonyloxy)-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid, 9.1 g of 1-trifluoromethylpiperazine and 200 ml of anhydrous dimethyl sulfoxide was heated with stirring in an autoclave at 150° to 160° C. for 18 hours under nitrogen gas flow at a pressure of 10 atms. After completion of the reaction, the solvent and excessive piperazine compound were removed by distillation under reduced pressure and a mixture of methanol and ethanol was added to the residue. The precipitates formed were collected by filtration and washed with ether. The crystals obtained were suspended in a mixture of 200 ml of water and 40 ml of a 10% aqueous hydrochloric acid solution and insoluble substances were removed by filtration. The filtrate was rendered neutral with saturated aqueous solution of sodium bicarbonate and purified through column chromatography using Amberlite LH-20 (a trade name for a product of Tokyo Organic Chemical Industries Ltd.) (eluent: water, ethanol). Recrystallization of the eluate from dimethylformamide gave 1.7 g of 8-(4-trifluoromethyl-1-piperazinyl)-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid as white rhombic crystals having a melting point of 300° C. or more.

Workup

  1. temperaturewas heated
  2. customAfter completion of the reaction
  3. customthe solvent and excessive piperazine compound were removed by distillation under reduced pressure
  4. additiona mixture of methanol and ethanol
  5. additionwas added to the residue
  6. customThe precipitates formed
  7. filtrationwere collected by filtration
  8. washwashed with ether
  9. customThe crystals obtained
  10. customwere removed by filtration
  11. custompurified through column chromatography
  12. customRecrystallization of the eluate from dimethylformamide

Sources & evidence

ORD record
ord-c8dda9e55ef5442fbfd339ac584821ef
Source dataset
uspto-grants-1983_11
Patent number
US04416884

Reaction notes

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