Citric Acid → 361343-20-6

HRID 396874Notes

Reaction equation

HRID 396874 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][S:12]/[C:11](=[CH:15]\[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[N:22]3[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]3)/[C:10]2=[O:29])[CH:5]=[CH:6][C:7]=1[Cl:8].[C:30]([OH:42])(=[O:41])[CH2:31][C:32]([CH2:37][C:38]([OH:40])=[O:39])([C:34]([OH:36])=[O:35])[OH:33]>C(O)(C)C>[C:30]([OH:42])(=[O:41])[CH2:31][C:32]([CH2:37][C:38]([OH:40])=[O:39])([C:34]([OH:36])=[O:35])[OH:33].[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][S:12]/[C:11](=[CH:15]\[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[N:22]3[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]3)/[C:10]2=[O:29])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

4

Reactant 2

HCID 311Citric AcidHCID 6914152Elzasonan

Product 1

HCID 6506050361343-20-6Yield 88%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
83.5 °C

Procedure

To an appropriate speck-free flask maintained under a nitrogen atmosphere, add Z-4-(3,4-dichlorophenyl)-2-[2-(4-methylpiperazin-1-yl)-benzylidene]-thiomorpholin-3-one (23.2 g, 51.8 mmol), citric acid (10.4 g, 54.4 mmol), and 603 mL of a speck-free aqueous isopropanol solution (1:1 v/v). A slurry formed and was heated to reflux (83-84° C.) affording a solution at approximately 70° C. The solution was further heated at reflux for 0.5 hours and then filtered hot. The filtrate was slowly cooled to 50-55° C. over 0.45 hours and then maintained at 50-55° C. for 1 hour. The slurry was cooled further to 0-5° C., granulated for 1-2 hours, and then filtered. The white crystalline solid was washed with 50% aqueous isopropanol (50 mL) and then dried at reduced pressure overnight to afford 29.1 grams of the title compound (88% yield).

Workup

  1. temperatureTo an appropriate speck-free flask maintained under a nitrogen atmosphere
  2. customA slurry formed
  3. temperaturewas heated
  4. customaffording a solution at approximately 70° C
  5. temperatureThe solution was further heated
  6. temperatureat reflux for 0.5 hours
  7. filtrationfiltered hot
  8. temperatureThe filtrate was slowly cooled to 50-55° C. over 0.45 hours
  9. temperaturemaintained at 50-55° C. for 1 hour
  10. temperatureThe slurry was cooled further to 0-5° C.
  11. filtrationfiltered
  12. washThe white crystalline solid was washed with 50% aqueous isopropanol (50 mL)
  13. customdried at reduced pressure overnight

Sources & evidence

ORD record
ord-9341dff0cffa46448cd2d64917577750
Source dataset
uspto-grants-2003_08
Patent number
US06608195B2

Reaction notes

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