Potassium Carbonate → Cilostazol

HRID 1795423Notes

Reaction equation

HRID 1795423 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 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 (49.09 g, 0.20 mol, 1.1 M), potassium carbonate (55.90 g, 0.40 mol, 2.2 M), sodium hydroxide (5.88 g, 0.15 mol, 0.8 M), sodium sulfite (1.5 g, 0.01 mol) and purified water (150 ml). The mixture of the reactants was heated at about 92° 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 mixture was introduced into a flask having a capacity of 1 L, methanol (150 mL) was added thereto and the resulting reaction mixture was refluxed with heating for about 2 hours. The mixture was cooled to the ambient temperature and the precipitated crystalline product was collected by filtration and washed with purified water (150 mL), methanol (90 mL), followed by purified water (150 mL), then dried at about 80° C. Thus, 62.14 g of cilostazol was obtained. Yield: 91.48%, Purity: 99.66%, 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. additionthe mixture was introduced into a flask
  8. additionwas added
  9. customthe resulting reaction mixture
  10. temperaturewas refluxed
  11. temperaturewith heating for about 2 hours
  12. temperatureThe mixture was cooled to the ambient temperature
  13. filtrationthe precipitated crystalline product was collected by filtration
  14. washwashed with purified water (150 mL), methanol (90 mL)
  15. customby purified water (150 mL)
  16. customdried at about 80° C

Sources & evidence

ORD record
ord-030c52aad81b42839753d9923920e074
Source dataset
uspto-grants-2006_04
Patent number
US07026486B2

Reaction notes

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