反应详情

3-[(Dimethylamino)methyl]-1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one hydrochloride (12 kg, 41 mol) and 2-methylimidazole (20.2 kg, 246 mol, 6 eq.) were suspended in mixture of water (120 L) and DMF (30 L). The reaction mixture was heated to reflux (100–102° C.) and stirred for 5 hours at this temperature. The reaction mixture was cooled to 5–10° C. and stirred for half an hour. The precipitated crude ondansetron base was filtered and washed with cold water (2×110 L) and dried under vacuum at 60° C. to give ondansetron base (10 kg, 83% yield) in 97.3% HPLC purity. The major impurity was the exomethylene carbazolone which amounted to 2.6% of the crude ondansetron mixture.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux (100–102° C.)
3. temperatureThe reaction mixture was cooled to 5–10° C.
4. stirringstirred for half an hour
5. customThe precipitated crude ondansetron base
6. filtrationwas filtered
7. washwashed with cold water (2×110 L)
8. customdried under vacuum at 60° C.