Cetirizine SynthesisUse: non-sedative antihistaminic
EP 58146 (patent)
Synthesis of Levocetirizine
The reaction of racemic cetiricine (I) with SOCl2 in toluene gives the acyl chloride (II), which is treated with ammonia to yield the corresponding racemic amide (III). The optical resolution of (III) by preparative chiral chromatography on a Chiralpak AD column affords the (R)-isomer (IV), which is treated with HCl in refluxing methanol to provide the chiral methyl ester (V). Finally, ester (V) is hydrolyzed with aqueous HCl to provide the chiral target compound. The hydrolysis of amide (IV) is not performed directly to the target acid owing to purification problems (separation of the ammonium chloride formed in the hydrolysis with HCl).
- Pflum, D.A.; et al.; A large-scale synthesis of enantiomerically pure cetirizine dihydrochloride using preparative chiral HPLC. Org Process Res Dev 2001, 5, 2, 110
- GB 2225321 (patent)
- EP 0617028 (patent)