Process for the production of piperidine derivatives
View Patent ↗The present invention relates to processes for preparing certain piperidine derivatives, including fexofenadine (F), the active ingredient in the non-sedating antihistamine sold in the U.S. under the designation “Allegra®”. This invention also relates to novel synthetic intermediates useful in the processes of the present invention.
1. A compound of formula (IX):
wherein alkyl is 1–6 carbon atoms.
2. The compound of claim 1 wherein the alkyl is methyl.
3. The compound of claim 1 wherein the alkyl is ethyl.
4. The process for preparing a piperidine derivative compound of formula (IX):
wherein alkyl is 1–6 carbon atoms comprising providing a compound of formula (VIII):
wherein alkyl is 1–6 carbon atoms, and converting the compound of formula (VIII) to the piperidine derivative compound of formula (IX) with a piperidine compound of formula (23):
5. The process according to claim 4 , wherein said providing comprises:
a) acylating a starting compound of formula (21):
wherein alkyl is 1–6 carbon atoms with a compound of formula (18)
under conditions effective to produce a mixture of regioisomers of formula (25):
wherein alkyl is 1–6 carbon atoms; and
b) recovering from the mixture of regioisomers the compound of formula (VIII):
wherein alkyl is 1–6 carbon atoms.
6. The process according to claim 5 wherein said recovering comprises crystallizing a regioisomeric salt of formula (VIIIa):
wherein alkyl is 1–6 carbon atoms and X + is a Lewis acid.
7. The process according to claim 6 wherein said recovering comprises crystallizing a regioisomeric salt of formula (VIIIa′):
wherein alkyl is 1–6 carbon atoms.
8. The process according to claim 5 wherein the alkyl is methyl.
9. The process according to claim 5 wherein the alkyl is ethyl.