loratidine

A) Synthesis of loratadine according to "Wittig reaction" between ethyl 4-

(diethoxyphosphoryl)piperidine-1-carboxylate (6.1.22) and ketone (6.1.18) in presence of lithium
diisopropylamide in xylene-THF media to give the β-hydroxy phosphonate (6.1.23), which was
further refluxed in xylene to give on thermal decomposition loratadine (6.1.3) [43].

B) For the synthesis of desloratadine (6.1.4), the carbamate group of loratadine (6.1.3) was further
cleaved under alkaline or acidic conditions to release the desired product "desloratadine" (6.1.4).

Cetirizine
C) for cetirizine.. The 1-(4-chlorophenylmethyl)-piperazine is alkylated with methyl (2-chloroethoxy)-
acetate in the presence of sodium carbonate and xylene solvent to produce acetate ester.

Saponification of the acetate ester is done by refluxing with potassium hydroxide in absolute ethanol to
afford a 56% yield of the potassium salt intermediate. This is then hydrolyzed with aqueous HCl and

extracted to give an 81% yield of the carboxylic acid product "cetirizine".

Fenoxidine
D)for fexofenadine... benzene (1) is acetated by 2-Methyl-2-propeny Acetate to obtain α,α-dimethyl
phenyl propyl alcohol acetate (2), which is then reacted with 4-butyl chloride to get 2-[4-(4-butyric
chloride)-phenyl]-2-methyl propyl acetate (3). After alkaline hydrolysis we get 2-(4-cyclopropyl
carbonyl)-phenyl-2-methyl propyl alcohol (4). Following oxidation of the alcohol to acid by potassium
permanganate, we get 2-(4-cyclopropyl carbonyl)-phenyl-2-methyl propionate acid (5). After
esterification of 5 by ethanol in acidic condition, 4-(4-chloral-1-carbonyl-butyl)-α,α-dimethyl phenyl acid
ethyl ester (6) is obtained. Then, the carbonyl is reduced to hydroxyl by sodium borohydride to get 4-(4-
chloro-1-hydroxyl-butyl)-α,α-dimethyl-ethyl phenyl acetate (7). Reaction with α,α-diphenyl-4-methanol
obtains 4-{1-hydroxyl-4-[4-(hydroxyl biphenyl methyl)-1-piperidyl]butyl}-α,α-dimethyl phenyl acetic acid
ethyl ester (8). Finally, the final product fexofenadine (9) is obtained after alkaline hydrolysis.