Potassium Carbonate → Cilostazol

HRID 748609Notes

Reaction equation

HRID 748609 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+]>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.S([O-])([O-])=O.[Na+].[Na+].O>[CH:13]1([N:19]2[C:23]([CH2:24][CH2:25][CH2:26][CH2:27][O:1][C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]4)=[N:22][N:21]=[N:20]2)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

7

Reactant 3

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

Product 1

HCID 2754CilostazolYield 87.7%

Reagents, catalysts & solvents 3

HCID 24437Sodium SulfiteCatalystHCID 70681Tetrabutylammonium ChlorideCatalystHCID 962WaterSolvent

Procedure

Into a flask having a capacity of 200 ml were introduced 12.00 g of 6-hydroxy-3,4-dihydrocarbostyril, 19.60 g of 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole, 8.20 g of 50% aqueous solution of tetrabutylammonium chloride, 12.20 g of potassium carbonate, 0.60 g of sodium sulfite and 60 ml of water. The content of the flask was heated under reflux for 8 hours with stirring. After the reaction, the reaction mixture was cooled to ambient temperature, and the deposited crude crystal was once collected by filtration. After washing the crystal firstly with 36 ml of methanol and then with 60 ml of water, the crystal was again introduced into a flask having a capacity of 200 ml and heated under reflux together with 84 ml of methanol for 2 hours. The solution thus obtained was cooled to 10° C. The crystal was collected by filtration, washed firstly with 24 ml of methanol and then with 24 ml of water, and dried at 80° C. Thus, 23.84 g (yield 87.7%) of 6-[4-(1-cyclohexyl-1,2,3,4-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril was obtained as a colorless needle-like crystalline product.

Workup

  1. customInto a flask having
  2. temperatureThe content of the flask was heated
  3. temperatureunder reflux for 8 hours
  4. customAfter the reaction
  5. filtrationthe deposited crude crystal was once collected by filtration
  6. washAfter washing the crystal firstly with 36 ml of methanol
  7. additionwith 60 ml of water, the crystal was again introduced into a flask
  8. temperatureheated
  9. temperatureunder reflux together with 84 ml of methanol for 2 hours
  10. customThe solution thus obtained
  11. temperaturewas cooled to 10° C
  12. filtrationThe crystal was collected by filtration
  13. washwashed firstly with 24 ml of methanol
  14. dry with materialwith 24 ml of water, and dried at 80° C

Sources & evidence

ORD record
ord-0d277f573da94913937f334c9aba83c6
Source dataset
uspto-grants-2008_07
Patent number
US07399864B2

Reaction notes

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