Potassium Carbonate → Cilostazol

HRID 1795425Notes

Reaction equation

HRID 1795425 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.[CH:13]1([N:19]2[C:23]([CH2:24][CH2:25][CH2:26][CH2:27]Cl)=[N:22][N:21]=[N:20]2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+]>S([O-])([O-])=O.[Na+].[Na+].CO>[CH:11]1[C:2]([O:1][CH2:27][CH2:26][CH2:25][CH2:24][C:23]2[N:19]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[N:20]=[N:21][N:22]=2)=[CH:3][C:4]2[CH2:5][CH2:6][C:7]([NH:8][C:9]=2[CH:10]=1)=[O:12]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27740406-Hydroxy-3,4-dihydro-2(1H)-quinolinoneHCID 112187395-(4-Chlorobutyl)-1-cyclohexyl-1H-tetrazole

Product 1

HCID 2754CilostazolYield 94.4%

Reagents, catalysts & solvents 2

HCID 24437Sodium SulfiteCatalystHCID 887MethanolSolvent

Conditions

Temperature
85 °C

Procedure

Into a reaction vessel having a capacity of 500 mL were introduced 6-hydroxy-3,4-dihydrocarbostyril (30 g, 0.18 mol), 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (49.1 g, 0.20 mol, 1.1 M), potassium carbonate (83.84 g, 0.61 mol, 3.3 M), sodium sulfite (1.5 g, 0.01 mol) and purified water (150 mL). The mixture of the reactants was heated at about 85° C. for about 6 hours with circulating by continuous disperser (pipeline homomixer T.K.ROBO MIX manufactured by TOKUSHUKIKA KOGYO CO. LTD.). After the completion of the reaction, the reaction mixture was cooled to around 50° C. and the deposited crude crystals were once collected by filtration. The crystals obtained were introduced into a flask having a capacity of 1 L and purified water (300 mL) was added thereto, then the crystals were washed with stirring at about 85° C. for about 15 minutes. After washing the crystals, the reaction mixture was cooled to around 50° C. and the precipitated crystals were collected by filtration. The crystals obtained were introduced into a flask again and methanol (210 mL) was added thereto, then the crystals were washed with stirring at about 25° C. for about 15 minutes. The reaction mixture was cooled to 10° C. or less, the precipitated crystalline product was collected by filtration and washed with methanol (60 mL), then dried at about 80° C. Thus, 62.79 g of cilostazol was obtained. Yield: 92.44%, Purity: 99.61%, m.p.: 158–159° C.

Workup

  1. customInto a reaction vessel having
  2. custompurified water (150 mL)
  3. additionThe mixture of the reactants
  4. additionMIX
  5. customAfter the completion of the reaction
  6. temperaturethe reaction mixture was cooled to around 50° C.
  7. filtrationthe deposited crude crystals were once collected by filtration
  8. customThe crystals obtained
  9. additionwere introduced into a flask
  10. custompurified water (300 mL)
  11. additionwas added
  12. washthe crystals were washed
  13. washAfter washing the crystals
  14. temperaturethe reaction mixture was cooled to around 50° C.
  15. filtrationthe precipitated crystals were collected by filtration
  16. customThe crystals obtained
  17. additionwere introduced into a flask again
  18. washthe crystals were washed
  19. stirringwith stirring at about 25° C. for about 15 minutes
  20. temperatureThe reaction mixture was cooled to 10° C. or less
  21. filtrationthe precipitated crystalline product was collected by filtration
  22. washwashed with methanol (60 mL)
  23. customdried at about 80° C

Sources & evidence

ORD record
ord-f8e7770d8e1c485b9baee84ed7f6fcd7
Source dataset
uspto-grants-2006_04
Patent number
US07026486B2

Reaction notes

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