Synthesis of Fexofenadin

Fexofenadin is an anti allergic drug.

1. Wellcome to My Presentation
Topics: Synthesis of
Fexofenadine
Md. Nuruzzaman
Roll NO. :13055085
M.Sc. Engineering 1
st
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 C
32
H
39
NO
4
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 4
th
step oxidation of the alcohol to acids by potassium permanganate to get 2-
(4-cyclopropyl carbonyl)-phenyl-2-methyl propionate acid.
oxidation
KMnO
4
2-(4-cyclopropyl carbonyl)-
phenyl-2-methyl propionate acid

7. Synthesis of Fexofenadine…
5. In the 5
th
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
C
2
H
5
OH
4-(4-chloral-1-carbonyl-butyl)-
α,α-dimethyl phenyl acid ethyl
ester

8. Synthesis of Fexofenadine…
6. In the 6
th
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
NaBH
4
4-(4-chloro-1-hydroxyl-butyl)-
α,α-dimethyl-ethyl phenyl
acetate

9. Synthesis of Fexofenadine…
7. In the 7
th
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