This document summarizes the 8-step synthesis of fexofenadine from benzene and methallyl. The steps involve Friedel–Crafts alkylation, hydrolysis, oxidation, esterification, reduction, and N-alkylation reactions. Specifically, the synthesis involves 1) acetating benzene with methyl allyl alcohol acetate, 2) reacting the product with 4-butyl chloride, 3) alkaline hydrolysis, 4) oxidation with potassium permanganate, 5) esterification with ethanol, 6) reducing the carbonyl to a hydroxyl with sodium borohydride, 7) reaction with α,α-diphenyl-4-piperidine methanol, and 8)

1. Wellcome to My Presentation
Topics: Synthesis of
Fexofenadine
Md. Nuruzzaman
Roll NO. :13055085
M.Sc. Engineering 1st
Semester
Dept. of Applied Chemistry & Chemical
Engineering
University of Rajshahi

2. Fexofenadine
Fexofenadine is an antihistamine pharmaceutical drug used in the treatment of
allergy. Therapeutically, fexofenadine is a selective peripheral H1-blocker. The
chemical name of fexofenadine is 4-{4-[4-(hydroxyl biphenyl methyl)-1-
Pepperdine]- 1-butyl hydroxyl acryl}-a,a-dimethyl phenyl acetic acid, with
molecular formula C32H39NO4 and molecular weight 501. It’s structural formula is
given below.
Fig. Structure of fexofenadine.

3. There are many fexofenadine synthesis routes ,according to W. Ronggeng et al,2013 for
the synthesis of fexofenadin benzene and methallyl are used as starting reactants, applying
steps of Friedel–Crafts alkylation reaction, hydrolysis, oxidation, esterification reaction,
and reduction reaction to obtain the intermediate product, followed by N-alkylation reaction
to obtain 4-{1-hydroxy-4-[4-(hydroxydiphenyl)- piperidine]butyl}-a,a-dimethylbenzene
acetate. Then, the final product fexofenadine is obtained upon hydrolysis. 8 steps are
involved in the synthesis of fexofendine according to this method;
1. In the first step benzene is acetated by methyl ally alcohol acetate to get α,α-dimethyl
phenyl propyl alcohol acetates.
Synthesis of Fexofenadine
benzene α,α-dimethyl phenyl propyl alcohol
acetates
methallyl

4. Synthesis of Fexofenadine…
2. In the 2nd step α,α-dimethyl phenyl propyl alcohol acetates react with 4-butyl chloride to
get 2-[4-(4-butyric chloride)-phenyl]-2-methyl propyl acetate.
+ 4-butyl chloride
2-[4-(4-butyric chloride)-phenyl]-
2-methyl propyl acetate

5. Synthesis of Fexofenadine…
3. In the 3rd step, by alkaline hydrolysis we get 2-(4-cyclopropyl carbonyl)-phenyl-2-
methyl propel alcohol.
Alkaline
hydrolysis
2-(4-cyclopropyl carbonyl)-phenyl-
2-methyl propel alcohol

6. Synthesis of Fexofenadine…
4. In the 4th
step oxidation of the alcohol to acids by potassium permanganate to get 2-
(4-cyclopropyl carbonyl)-phenyl-2-methyl propionate acid.
oxidation
KMnO4
2-(4-cyclopropyl carbonyl)-
phenyl-2-methyl propionate acid

7. Synthesis of Fexofenadine…
5. In the 5th
step esterification takes place by adding ethanol in acidic condition, as a
result 4-(4-chloral-1-carbonyl-butyl)-α,α-dimethyl phenyl acid ethyl ester is obtained.
Esterification
C2H5OH
4-(4-chloral-1-carbonyl-butyl)-
α,α-dimethyl phenyl acid ethyl
ester

8. Synthesis of Fexofenadine…
6. In the 6th
step, the carbonyl is reduced to hydroxyl by sodium borohydride to get
4-(4-chloro-1-hydroxyl-butyl)-α,α-dimethyl-ethyl phenyl acetate.
Reduction
NaBH4
4-(4-chloro-1-hydroxyl-butyl)-
α,α-dimethyl-ethyl phenyl
acetate

9. Synthesis of Fexofenadine…
7. In the 7th
step, reaction with α, α-diphenyl-4-piperidine methanol obtains 4-{1-
hydroxyl-4-[4-(hydroxyl biphenyl methyl)-1-piperidyl]butyl}-α,α-dimethyl phenyl
acetic acid ethyl ester.
α, α-diphenyl-4-
piperidine methanol
4-{1-hydroxyl-4-[4-(hydroxyl biphenyl
methyl)-1-piperidyl]butyl}-α,α-
dimethyl phenyl acetic acid ethyl ester

10. Synthesis of Fexofenadine…
8. Finally, the final product fexofenadine is obtained after Alkaline hydrolysis.
Alkaline
hydrolysis
Fexofenadin

11. THANK YOU