viloxazine

viloxazine Property

Melting point:

176-179 °C

Boiling point:

379.83°C (rough estimate)

Density 

1.0942 (rough estimate)

refractive index 

1.5000 (estimate)

pka

pKa 8.1 (Uncertain)

form 

Oil

color 

Colorless to light yellow

InChI

InChI=1S/C13H19NO3/c1-2-15-12-5-3-4-6-13(12)17-10-11-9-14-7-8-16-11/h3-6,11,14H,2,7-10H2,1H3

InChIKey

YWPHCCPCQOJSGZ-UHFFFAOYSA-N

SMILES

N1CCOC(COC2=CC=CC=C2OCC)C1

Hazard and Precautionary Statements (GHS)

viloxazine Chemical Properties,Usage,Production

Originator

Vivalan,I.C.I. ,UK,1974

Uses

Viloxazine is approved by the FDA for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in paediatric patients (6-17 years old).

Definition

ChEBI: 2-[(2-ethoxyphenoxy)methyl]morpholine is an aromatic ether.

Manufacturing Process

2-Ethoxyphenol is first reacted with epichlorohydrin to give 1,2-epoxy-3-(o- ethoxyphenoxy)-propane.
A mixture of crude (83%) 1,2-epoxy-3-(o-ethoxyphenoxy)propane (19.4 grams), 70.5 grams 2-aminoethyl hydrogen sulfate, 40.0 grams sodium hydroxide, 400 ml ethanol and 200 ml water is stirred at 60°C for 18 hours and is then evaporated to dryness. The residue is dissolved in 200 ml water and the mixture is extracted three times with 150 ml of diethyl ether each time. The combined extracts are dried over magnesium sulfate and evaporated to dryness, The crude product (21.5 grams) is dissolved in isopropanol (20 ml), 10.5 ml concentrated aqueous hydrochloric acid and 75 ml ethyl acetate are added and the mixture is cooled. The mixture is filtered and there is thus obtained as solid product 2-(o-ethoxyphenoxymethyl) morpholine hydrochloride, MP 179° to 182°C (8.6 grams; 38% yield based on total epoxide used), according to US Patent 3,712,890.

Therapeutic Function

Psychotropic

Mechanism of action

Viloxazine works by inhibiting the reuptake of norepinephrine and possibly through interaction with 5- hydroxytryptamine receptors.

Synthesis

Viloxazine was synthesized via a four-step process. In the first step, 2-ethoxyphenol (9.1) was reacted with epichlorohydrin (9.2) in the presence of potassium carbonate and a phase transfer catalyst (n-Bu4NHSO4) to produce the epoxide (9.3) in almost equivalent yield. Next, the epoxide (9.3) was reacted with 2-aminoethylsulfuric acid (9.4) in the presence of a strong base to trigger the opening of the epoxide ring and subsequent cyclization to form 2-morpholine (9.5) in 40% yield. Finally, the free basic amine (9.5) was treated with concentrated hydrochloric acid, and the prepared salt was recrystallized from a water/isopropanol/ethyl acetate mixed solvent to obtain Viloxazine hydrochloride (9) with a purity of 99%.