- Production Route of Risperidone
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(CAS NO.: ), with other name of 4H-Pyrido(1,2-a)pyrimidin-4-one, 6,7,8,9-tetrahydro-3-(2-(4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl)ethyl)-2-methyl-, could be produced through many synthetic methods.
Following is one of the synthesis routes:
The Friedel-Crafts condensation of 1,3-di (I) with 1-acetylpiperidine-4-carbonyl chloride (II) by means of AlCl3 in dichloromethane gives 1-acetyl-4-(2,4-difluorobenzoyl)piperidine (III), which is hydrotyzed with refluxing 6N HCl to yield 4-(2,4-difluorobenzoyl)piperidine (IV). The reaction of (IV) with hydroxylamine in refluxing ethanol affords the corresponding oxime (V), which is cyclized by means of KOH in boiling water giving 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (VI). Finally, this compound is condensed with 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (VII) by means of K2CO3 and Kl in a variety of solvents.
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