Potassium Carbonate → Cilostazol

HRID 1795424Notes

Reaction equation

HRID 1795424 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+].[OH-].[Na+]>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

7

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 27740406-Hydroxy-3,4-dihydro-2(1H)-quinolinoneHCID 112187395-(4-Chlorobutyl)-1-cyclohexyl-1H-tetrazole

Product 1

HCID 2754CilostazolYield 93.4%

Reagents, catalysts & solvents 2

HCID 24437Sodium SulfiteCatalystHCID 887MethanolSolvent

Conditions

Temperature
92 °C

Procedure

Into a flask having a capacity of 200 mL were introduced 6-hydroxy-3,4-dihydrocarbostyril (12 g, 0.07 mol), 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (19.64 g, 0.08 mol), potassium carbonate (22.36 g, 0.16 mol), sodium hydroxide (2.35 g, 0.05 mol), sodium sulfite (0.6 g, 0.004 mol) and purified water (60 mL). The mixture of the reactants was heated at about 92° C. for about 6 hours. 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 and purified water (120 mL) was added thereto, then the crystals were washed with stirring at about 85° C. for about 15 minutes. 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 (84 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 (24 mL), then dried at about 80° C. Thus, 24.15 g of cilostazol was obtained. Yield: 88.88%, Purity: 99.50%, m.p.: 158–159° C.

Workup

  1. customInto a flask having
  2. custompurified water (60 mL)
  3. additionThe mixture of the reactants
  4. customAfter the completion of the reaction
  5. temperaturethe reaction mixture was cooled to around 50° C.
  6. filtrationthe deposited crude crystals were once collected by filtration
  7. customThe crystals obtained
  8. additionwere introduced into a flask
  9. custompurified water (120 mL)
  10. additionwas added
  11. washthe crystals were washed
  12. temperatureThe reaction mixture was cooled to around 50° C.
  13. filtrationthe precipitated crystals were collected by filtration
  14. customThe crystals obtained
  15. additionwere introduced into a flask again
  16. washthe crystals were washed
  17. stirringwith stirring at about 25° C. for about 15 minutes
  18. temperatureThe reaction mixture was cooled to 10° C. or less
  19. filtrationthe precipitated crystalline product was collected by filtration
  20. washwashed with methanol (24 mL)
  21. customdried at about 80° C

Sources & evidence

ORD record
ord-47363576182247baa64c7e33bdf4802d
Source dataset
uspto-grants-2006_04
Patent number
US07026486B2

Reaction notes

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