Potassium Carbonate → Cilostazol

HRID 1795427Notes

Reaction equation

HRID 1795427 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 94%

Reagents, catalysts & solvents 2

HCID 24437Sodium SulfiteCatalystHCID 887MethanolSolvent

Conditions

Temperature
10 °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), purified water (36 mL) and isopropanol (3.6 mL), and the reaction was conducted for about 6 hours under reflux. After the completion of the reaction, the reaction mixture was cooled to around 10° C., and the precipitated crystals were 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, 24.31 g of cilostazol was obtained. Yield: 89.47%, Purity: 99.45%, m.p.: 158–159° C.

Workup

  1. customInto a flask having
  2. custompurified water (36 mL) and isopropanol (3.6 mL)
  3. temperatureunder reflux
  4. customAfter the completion of the reaction
  5. filtrationthe precipitated crystals were collected by filtration
  6. customThe crystals obtained
  7. additionwere introduced into a flask
  8. custompurified water (120 mL)
  9. additionwas added
  10. washthe crystals were washed
  11. temperatureThe reaction mixture was cooled to around 50° C.
  12. filtrationthe precipitated crystals were collected by filtration
  13. customThe crystals obtained
  14. additionwere introduced into a flask again
  15. washthe crystals were washed
  16. stirringwith stirring at about 25° C. for about 15 minutes
  17. temperatureThe reaction mixture was cooled to 10° C. or less
  18. filtrationthe precipitated crystalline product was collected by filtration
  19. washwashed with methanol (24 mL)
  20. customdried at about 80° C

Sources & evidence

ORD record
ord-fee4473f12e240f9b6623fa8cfa0c024
Source dataset
uspto-grants-2006_04
Patent number
US07026486B2

Reaction notes

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