Toluene → Cilostazol

HRID 748608Notes

Reaction equation

HRID 748608 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+].C1(C)C=CC=CC=1>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.S([O-])([O-])=O.[Na+].[Na+].CO.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

9

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 27740406-Hydroxy-3,4-dihydro-2(1H)-quinolinoneHCID 112187395-(4-Chlorobutyl)-1-cyclohexyl-1H-tetrazole

Product 1

HCID 2754CilostazolYield 95%

Reagents, catalysts & solvents 4

HCID 24437Sodium SulfiteCatalystHCID 70681Tetrabutylammonium ChlorideCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Into a three-necked flask having a capacity of 300 ml were introduced 10.00 g of 6-hydroxy-3,4-dihydrocarbostyril, 16.36 g of 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole, 10.16 g of potassium carbonate, 3.00 g of tetrabutylammonium chloride, 0.05 g of sodium sulfite, 30 ml of toluene and 50 ml of water. The content of the flask was heated under reflux for 8 hours with stirring. After cooling the reaction mixture to ambient temperature, the deposited crystalline product was collected by filtration and washed with 50 ml of water. Then, the crude crystal thus obtained was introduced into 70 ml of 90% methanol cooled to 5° C., and stirred at 5° C. for 10 minutes for the sake of washing. The crystal was collected by filtration and further washed on the suction filter with 20 ml of 90% methanol cooled to 5° C. The crystal was dried to obtain 21.46 g (yield 95%) of 6-[4-(1-cyclohexyl-1,2,3,4-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril as a colorless needle-like crystalline product.

Workup

  1. customInto a three-necked flask having
  2. temperatureThe content of the flask was heated
  3. temperatureunder reflux for 8 hours
  4. filtrationthe deposited crystalline product was collected by filtration
  5. washwashed with 50 ml of water
  6. customThen, the crude crystal thus obtained
  7. temperaturecooled to 5° C.
  8. stirringstirred at 5° C. for 10 minutes for the sake
  9. washof washing
  10. filtrationThe crystal was collected by filtration
  11. washfurther washed on the suction
  12. filtrationfilter with 20 ml of 90% methanol
  13. temperaturecooled to 5° C
  14. customThe crystal was dried

Sources & evidence

ORD record
ord-ee150343ca374b5cb81232b57330e138
Source dataset
uspto-grants-2008_07
Patent number
US07399864B2

Reaction notes

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