Process for the solid phase synthesis of aldehyde, ketone, oxime, amine, hydroxamic acid and .alpha..beta.-unsaturated carboxylic acid and aldehyde compounds
AssigneeAventis Pharmaceuticals Products Inc.
InventorsJoseph M. Salvino, George C. Morton, Helen J. Mason, Richard F. Labaudiniere
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Abstract
This invention is directed to a process for the solid phase synthesis of aldehyde, ketone, oxime, amine, hydroxamic acid and .alpha.,.beta.-unsaturated carboxylic acid and aldehyde compounds and to polymeric hydroxylamine resin compounds useful therefor.
Claims44
A process for the preparation of a ketone compound of formula ##STR116## wherein R.sub.c and R.sub.a are independently aliphatic or aromatic comprising
- (a) reacting an N-alkylated polymeric hydroxamic acid resin compound of formula ##STR117## wherein is a solid support, L is absent or a linking group and R.sub.a and R.sub.b are independently aliphatic or aryl, with an organometallic reagent of formula R.sub.c M wherein R.sub.c is an aliphatic or aryl anion and M is a metal cation;
- and
- (b) liberating the ketone compound from the resin.
A process for the preparation of an aldehyde compound of formula R.sub.a CHO wherein R.sub.a is aliphatic or aryl,
- comprising
- (a) reacting an N-alkylated polymeric hydroxamic acid resin compound of formula ##STR121## wherein is a solid support, L is absent or a linking group and R.sub.a and R.sub.b are independently aliphatic or aryl;
- with a reducing agent;
- and
- (b) liberating the aldehyde compound from the resin.
A process for the preparation of a N-alkylated polymeric hydroxamic acid resin compound of formula ##STR125## wherein is a solid support, L is absent or a linking group and R.sub.a and R.sub.b are independently aliphatic or aryl;
- comprising
- (a) coupling a carboxylic acid compound of formula R.sub.a CO.sub.2 H with a polymeric hydroxylamine resin compound of formula ##STR126## to form a polymeric hydroxamic acid resin compound of formula ##STR127## (b) reacting the polymeric hydroxamic acid resin compound with an alkylating agent of formula R.sub.b LG wherein LG is a leaving group.
A process for the preparation of a N-alkylated polymeric hydroxamic acid resin compound of formula ##STR131## wherein is a solid support, L is absent or a linking group and R.sub.a and R.sub.b are independently aliphatic or aryl;
- comprising
- (a) reacting a N-protected polymeric hydroxamic acid resin compound of formula ##STR132## wherein P is an amine protecting group, with an alkylating agent of formula R.sub.b LG wherein LG is a leaving group, to form a polymeric N-protected N-alkylated hydroxylamine resin compound of formula ##STR133## (b) removing the amine protecting group to form a polymeric N-alkylated hydroxylamine resin compound of formula ##STR134## (c) coupling the polymeric N-alkylated hydroxylamine resin compound with a carboxylic acid compound of formula R.sub.a CO.sub.2 H.
A polymeric N-protected hydroxylamine resin compound of formula ##STR138## wherein is a solid support;
- L is absent or a linking group;
- and
- P is an amine protecting group, provided that P is other than 4-methoxybenzyl or 2,4-dimethoxybenzyl.
Dependencies are inferred from the claim text.