反応 #340253

反応方程式

clopidogrel

potassium hydrogen sulfate

acetone

→

clopidogrel hydrogen sulfate

収率 42.0%

溶媒

water

反応条件

後処理

1. 1
   workup.STIRRINGfurther stirred for 30 minutes
2. 2
   ろ過filtered
3. 3
   workup.DISTILLATIONThe filtrate was distilled at 50-55° C.
4. 4
   workup.ADDITIONBenzene (10 mL) was added to the reaction mixture
5. 5
   workup.DISTILLATIONdistilled at 90-95° C.
6. 6
   workup.ADDITIONdi-isopropyl ether (20 mL) was added
7. 7
   workup.STIRRINGstirred at 25-30° C. for 1 hour
8. 8
   ろ過filtered
9. 9
   workup.DISSOLUTIONwas dissolved in dichloromethane (25 mL)
10. 10
    workup.DISTILLATIONdistilled under reduced pressure (5-10 mm)

実験手順

To a stirred suspension of clopidogrel base (3.83 g, 0.0119 mole) in water (3 mL) was added potassium hydrogen sulfate (1.62 g, 0.0119 mole) at 25-30° C. The reaction mixture was stirred for 15 minutes and acetone (25 mL) was added, further stirred for 30 minutes and filtered. The filtrate was distilled at 50-55° C. under reduce pressure (5-10 mm). Benzene (10 mL) was added to the reaction mixture and distilled at 90-95° C., di-isopropyl ether (20 mL) was added and stirred at 25-30° C. for 1 hour and filtered. The semi sold material was dissolved in dichloromethane (25 mL) and distilled under reduced pressure (5-10 mm) to give clopidogrel hydrogen sulfate (2.1 g). The amorphous form was similarly characterized by XRD, DSC, IR, chemical purity (HPLC)>99% and chiral purity (chiral HPLC) 99.5% (e.e.), % water 3.0, m.p. 94-98° C. (softens).

出典