Chiral intermediate, process for producing the same and its use in the manufacture of tolterodine, fesoterodine, or the active metabolite thereof
The compound of formula (I): is provided. It may be produced by subjecting a compound of formula (IV) to a reduction reaction wherein R represents hydrogen, straight or branched C 1 -C 6 alkyl. This compound is a valuable intermediate which may be used in the synthesis of fesoterodine, tolterodine, its active metabolite, and related compounds.
1. A compound that is the essentially pure 4R-diastereomer of formula (I):
2. The compound of claim 1 in crystalline form.
3. A process for producing a compound of formula (I)
wherein a compound of formula (IV)
is subjected to a reduction reaction;
wherein R represents hydrogen or a straight or branched C 1 -C 6 alkyl group wherein the reducing agent is a dialkylaluminum hydride, and the reduction is performed with a reducing agent in a molar ratio [reducing agent/compound of formula (IV)] of about 3 or more.
4. The process of claim 3 , wherein the reducing agent is a diisobutylaluminum hydride.
5. The process of claim 3 , wherein the reducing agent is diisobutylaluminum hydride and the reaction is conducted at a temperature of −20° C. to 0° C.
6. The process of claim 5 , wherein the reaction is conducted at a temperature of −20° C. to −5° C.
7. A process for producing the active metabolite of tolterodine or phenolic monoesters of formula (III):
wherein R1 is selected from the group consisting of hydrogen, an optionally substituted straight, branched or cyclic C 1 -C 6 alkyl group and an optionally substituted aryl group, or a salt thereof,
comprising converting the essentially pure 4R-diastereomer of the compound of formula I
into the active metabolite of tolterodine or the phenolic monoesters of formula (III).
8. The process of claim 7 , wherein fesoterodine or its salts is produced.
9. The process of claim 7 , wherein fesoterodine hydrogen fumarate is produced.