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US 6,444,822 B1Granted
Process for the preparation of 3-substituted 4-phenyl-piperidine derivative
AssigneeChemi S.p.A.
InventorsLorenzo De Ferra, Pietro Massardo, Oreste Piccolo, Giorgio Cignarella
Life of this patent
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Abstract
Described herein is the process for the preparation of 3-substituted 4-phenyl-piperidine derivatives of formula (I) in which X is selected from H and F, and R is selected from the group consisting of H, C1-C6 alkyl, C3-C6 alkenyl, and benzyl, comprising three steps starting from the monoamide of malonic acid and cinnamic aldehyde, or derivatives thereof.
Claims9
A process for the preparation of 3-substituted 4-phenyl-piperidine derivatives of formula(I)
- In which X is selected from H and F, and R is selected from the group consisting of H, C1-C6 alkyl, C3-C6 alkenyl, and benzyl, comprising the following steps:
- a) Michael addition between the formula (II) cinnamic aldehyde and the amide of formula (III) in which R1 is selected from the group consisting of C1-C6 alkyl, C3-C6 alkenyl, and benzyl, to obtain the formula (IV) 2-keto-3-carboxyalkyl-4-phenyl-6-hydroxy-piperidine, optionally enriched in the (3S,4R) isomer by using a suitable chiral catalyst:
- b) reduction of the formula (IV) 2-keto-3-carboxyalkyl-4-phenyl-6-hydroxy-piperidine coming from step a) to obtain the 3-hydroxymethyl-4-phenyl-piperidine of formula (V):
- c) reaction of 3-hydroxymethyl-4-phenyl-piperidine of formula (V) coming from step b) with sesamol (VI) to obtain the formula (I) 3-[(1,3-benzodioxol-5-yloxoli)methyl]-4-phenyl-piperidine:
1 more element
Compound according to formula (IV)
- in which R1 is selected from the group consisting of C1-C6 alkyl, C3-C6 alkenyl, and benzyl, X is selected from H and F, and R is selected from the group consisting of H, C1-C6 alkyl, C3-C6 alkenyl, and benzyl.
Compound of formula (IV′)
- in which R1 is selected from the group consisting of C1-C6 alkyl, C3-C6 alkenyl, and benzyl, and X is selected from H and F.
Dependencies are inferred from the claim text.