Claims
- 1. A process for the preparation of loratadine consisting of reacting, in an organic solvent and in the presence of a tertiary amine, 8-chloro-5,6-dihyrobenzo[5,6]cyclohepta[1,2-b]pyridin-11-one, of formula VII ##STR7## and ethyl 4-oxopiperidine-1-carboxylate of formula IV ##STR8## with low-valent titanium species.
- 2. The process of claim 1, wherein the low-valent titanium species are generated by reduction of titanium tetrachloride with zinc dust.
- 3. The process of claim 2, wherein the preparation of the low-valent titanium species is carried out at a temperature comprised between 10 and -20.degree. C.
- 4. The process of claim 3, wherein the preparation of the low-valent titanium species is carried out at a temperature comprised between 0 and -5.degree. C.
- 5. The process of claim 1, wherein the organic solvent used is an ether.
- 6. The process of claim 5, wherein such ether is diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane.
- 7. The process of claim 1, wherein the tertiary amine is triethylamine, ethyldiisopropylamine, tributylamine, or pyridine.
- 8. The process of claim 7, wherein the tertiary amine is pyridine.
- 9. The process of claim 1, wherein the reaction of the compound of formula VII and the compound of formula IV is carried out at a temperature comprised between 30.degree. C. and the reflux temperature of the used solvent.
- 10. The process of claim 9, wherein the reaction is carried out at a temperature comprised between 30 and 50.degree. C.
- 11. The process of claim 1, wherein the reaction time for the reaction of the compound of formula VII and the compound of formula IV is comprised between 4 and 72 hours.
- 12. The process of claim 11, wherein the reaction time is comprised between 6 and 24 hours.
- 13. A process to obtain loratadine consisting of the steps of:
- a) preparing low-valent titanium species by reduction of titanium tetrachloride with zinc dust in an organic solvent,
- b) adding a tertiary amine,
- c) adding a mixture of 8-chloro-5,6-dihydrobenzo[5,6]-cyclohepta[1,2-b]pyridin-11-one and ethyl 4-oxopiperidine-1-carboxylate and heating the reaction mixture for the required time to complete the reaction, and
- d) isolating loratadine from the reaction mixture.
Parent Case Info
This application claims benefit from U.S. Provisional Application Ser. No. 60/048,083, filed on May 30, 1997.