Patent ID: 7629466
Filing Date: 2009-12-08
Classification: A61P,C07D

Abstract:
1. A method for preparing (R)-quinuclidine-3-yl 6-((3S,4R)-4-(4-amino-5-chloro-2-methoxybenzamido)-3-methoxypiperidin-1-yl)hexanoate or a salt thereof, comprising: 1) optionally converting a compound of formula (I′)  to a salt, wherein R is (C 2) converting the compound of formula (I′) or its salt to a compound of formula (II′)  or its salt, respectively, wherein X 3) treating the compound of formula (II′) with an alkali metal hydroxide or hydride to yield a compound of formula (III′) 4) producing a chiral salt of III′ by treating the compound of formula (III′) with about 0.5 equivalents of a chiral resolving agent and isolating the chiral salt of III′; 5) optionally recrystallizing the product of 4; 6) basifying the product of 4 or 5 to yield the free base form of the product of 4 or 5; 7) contacting the product of 6 with a (C  wherein R′ is (C 8) treating the product of 7 with (R)-quinuclidine-3-ol and a Lewis acid in an organic solvent to yield a compound of formula (V′) 9) deprotecting the 4-amino group of the product of 8 to yield (R)-quinuclidine-3-yl 6-[(3S,4R)-4-amino-3-methoxypiperidin-1-yl]hexanoate; 10) acylating the product of 9 with 4-amino-5-chloro-2-methoxybenzoic acid; 11) optionally converting the product of 10 to a salt.