(+-)-2-Butanol → Olanzapine

Participants

Reaction Conditions

Reaction Steps

4-Amino-2-methyl-10H-thieno-[2,3-b][1,5]benzodiazepine (100 g, 0.38 mol), N-methylpiperazine (250 mL, 2.5 vol) and 2-butanol (200 mL, 2 vol) were charged into a three-necked round bottom flask equipped with a reflux condenser, overhead stirrer, and thermometer. The reaction mixture was heated to reflux at 118° C. under a nitrogen atmosphere and refluxed overnight. The reaction mixture was allowed to cool to below 55° C. whereupon water (300 mL, 3 volumes) was added to precipitate out the solid. It was isolated by Buchner filtration and the light yellow solid was washed twice with 25% aqueous 2-butanol (100 mL) and then once with 2-butanol (100 mL) and dried to provide olanzapine in 84% yield (98.7 g).

Provenance & Evidence