反応 #340252

反応方程式

clopidogrel

potassium hydrogen sulfate

acetone

→

clopidogrel hydrogen sulfate

収率 92.1%

溶媒

water

反応条件

後処理

1. 1
   workup.STIRRINGstirred further for 30 minutes
2. 2
   ろ過filtered
3. 3
   ろ過Insoluble solid was filtered
4. 4
   workup.DISTILLATIONThe filtrate was distilled at 50-55° C. under reduced pressure (5-10 mm)
5. 5
   workup.ADDITIONDichloromethane (380 mL) was added
6. 6
   workup.DISTILLATIONdistilled at 50-55° C
7. 7
   workup.ADDITIONby adding dichloromethane (350 mL)
8. 8
   その他was removed

実験手順

To a stirred suspension of clopidogrel base (38.31 g, 0.119 mole) in water (30 mL), was added potassium hydrogen sulfate (32.3 g, 0.237 mole) at 25-30° C. The reaction mixture was stirred for 15 minutes and acetone (250 mL) was added, stirred further for 30 minutes and filtered. Insoluble solid was filtered. The filtrate was distilled at 50-55° C. under reduced pressure (5-10 mm). Dichloromethane (380 mL) was added and distilled at 50-55° C. This operation was repeated twice by adding dichloromethane (350 mL), and finally traces of water was removed under reduce pressure (5-10 mm) to give amorphous clopidogrel hydrogen sulfate (46 g). The amorphous form was similarly characterized by XRD, DSC, IR, chemical purity (HPLC)>99% and chiral purity (chiral HPLC) 99.8% (e.e.), % water 1.91, m.p. 132-135° C. (softens).

出典