FIELD OF THE INVENTION
The present invention relates to a process for the preparation of Viloxazine
Hydrochloride (1) having a purity greater than 99.5% by High-performance liquid
chromatography (HPLC). It further relates to crystalline form of Viloxazine
5 Hydrochloride (1).
BACKGROUND OF THE INVENTION:
Viloxazine hydrochloride is used for the treatment of Attention-deficithyperactivity-disorder (ADHD) in pediatric patients 6 to 17 years of age. The drug
was approved in US under the brand name QELBREE® 10 . Viloxazine hydrochloride
is a white to off-white powder. Viloxazine hydrochloride is soluble in water, 0.1N
HCl and aqueous solutions of pH 9.5 and lower
The synthesis of Viloxazine hydrochloride (1) has been reported in prior art patents
and the process of which are hereby incorporated as reference in their entirety.
US3712890 discloses preparation of Viloxazine hydrochloride, which involves
reacting 1,2-epoxy-3-(o-ethoxy phenoxy) propane and 2-aminoethyl hydrogen
20 sulphate in presence of base and ethanol.
US9403783B2 discloses preparation of Viloxazine hydrochloride, which involves
reacting 1-(2-ethoxyphenoxy)-2,3-epoxypropane with N-benzyl-aminoethanol to
form diol intermediate. Reacting diol intermediate with cyclizing agent in presence
25 of base to form N-benzyl Viloxazine followed by deprotection to obtain Viloxazine
or pharmaceutically acceptable salt.
3
OBJECTIVE OF THE INVENTION
One objective of the present invention is to provide a process for the preparation of
Viloxazine hydrochloride (1) having purity greater than 99.5% by Highperformance liquid chromatography (HPLC).
5
Another objective of the present invention is to provide crystalline form of
Viloxazine Hydrochloride (1).
SUMMARY OF THE INVENTION
10 Accordingly, one embodiment of the present invention relates to a process for the
preparation of Viloxazine hydrochloride (1) with a purity greater than 99.5% by
High-performance liquid chromatography (HPLC), which comprises.
a) reacting 2-ethoxyphenol (5) with 2-(chloromethyl) oxirane (4) in presence of
suitable base to obtain 2-((2-Ethoxyphenoxy) methyl) oxirane (3);
15 b) reacting 2-((2-Ethoxyphenoxy) methyl) oxirane (3) with 2-Aminoethyl
hydrogen sulfate (2) in a solvent and in presence of suitable base to obtain
Viloxazine hydrochloride (1); and
c) purifying Viloxazine hydrochloride.
20 In another embodiment, the present invention relates to the process for the
purification of Viloxazine hydrochloride (1), which comprises,
a) dissolving crude viloxazine hydrochloride in one or more solvent (s);
b) heating the reacting mass to 75-80°C and stirring;
c) adding activated charcoal and stirring;
25 d) filtering the reaction mass; and
e) isolating pure Viloxazine hydrochloride (1)

We claim:
1. A process for the preparation of Viloxazine hydrochloride of formula (1),
which comprises:
a) reacting 2-ethoxyphenol of formula (5)
5
with 2-(chloromethyl) oxirane of formula (4)
in the presence of a base to obtain 2-((2-Ethoxyphenoxy) methyl) oxirane
10 of formula (3);
b) reacting the compound of formula (3) with 2-Aminoethyl hydrogen sulfate
of formula (2)
15 in presence of a base to obtain Viloxazine hydrochloride (1); and
c) purifying Viloxazine hydrochloride (1)
11
2. The process as claimed in claim 1, wherein base used in step (a) is an alkali
metal carbonate selected from lithium carbonate, sodium carbonate,
potassium carbonate or caesium carbonate; in step b) is an alkali metal
hydroxide selected from lithium hydroxide, sodium hydroxide or potassium
5 hydroxide.
3. The process as claimed in claim 1, wherein the solvent used in step b) is an
alcoholic solvent such as methanol, ethanol, isopropanol, t-amyl alcohol, tbutyl alcohol or hexanol.
4. A process for the purification of Viloxazine hydrochloride (1), which
10 comprises,
a) dissolving crude viloxazine hydrochloride in one or more solvent (s);
b) heating the reacting mass of step a).
c) adding activated charcoal;
d) cooling the reaction mass of step c); and
15 e) isolating pure Viloxazine hydrochloride (1).
5. The process as claimed in claim 4, wherein the solvent used in step (a) is an
alcoholic solvent such as methanol, ethanol, isopropanol, t-amyl alcohol, tbutyl alcohol or hexanol; ester solvent such as ethyl acetate, methyl acetate, nbutyl acetate, isobutyl acetate, sec-butyl acetate, or isopropyl acetate; or water
or a mixture thereof.
6. The process as claimed in claim 4, wherein the heating temperature in step b)
ranges from 75 °C to 90 °C.
7. The process as claimed in claim 4, wherein the cooling temperature in step d)
ranges from 0 °C to 5 °C.