Method for preparing disubstituted piperidine and intermediates
View Patent ↗The disclosure relates to a method for preparing a compound of formula (I), wherein P 1 and P 2 are groups protecting the carboxylic acid and oxyamine functions, starting from pyroglutamic acid (S). The disclosure also relates to novel intermediates.
1. A method for preparing the compound of formula (I)
wherein P 1 and P 2 represent groups protecting the carboxylic acid and oxyamine functions, comprising a beta-ketosulfoxonium compound of formula:
wherein P 1 is as defined here above and P 3 represents an amine protecting group, is treated with a reagent generating HCl, in order to obtain the compound of formula:
wherein P 1 and P 2 are as defined here above, which is treated without isolating it, with hydroxylamine derivative, in order to obtain the compound of formula:
wherein P 1 and P 3 are as defined here above and P 2 represents a protecting group of the oxime, the amine of which is de-protected by the action of an acid, in order to obtain the compound of formula:
wherein P 1 and P 2 are defined as here above, which is cyclized by the action of a base, in order to obtain the compound of formula:
wherein P 1 and P 2 are defined as here above, the oxime function of which is reduced by the action of a reducing agent, in order to obtain the expected compound of formula (I) which, if desired, is salified by the action of an acid.
2. The method according to claim 1 , wherein P 1 represents a benzyl group.
3. The method according to claim 1 , wherein P 3 represents a tert-butoxy-carbonyl group.
4. The method according to claim 1 , wherein P 2 represents a benzyl group.
5. The method according to claim 1 , wherein the compound of formula (b) is treated with lithium chloride in the presence of methane sulfonic acid.
6. The method according to claim 1 , wherein the amine of the compound of formula (III) is de-protected by the action of methane sulfonic acid, without prior isolation of this compound.
7. The method according to claim 1 , wherein the cyclization of the compound of formula (IV) is carried out by the action of sodium bicarbonate.
8. A compound of formula
wherein P 1 represents a group protecting the carboxylic acid function, P 2 represents a group protecting the oxyamine function and P 3 represents an amine protecting group.
9. A compound of formula (IV):
wherein P 1 represents a group protecting the carboxylic acid function and P 2 represents a group protecting the oxyamine function.
10. A compound of formula (V):
wherein P 1 represents a group protecting the carboxylic acid function and P 2 represents a group protecting the oxyamine function.