2-[(2-ethoxyphenoxy)methyl]morpholine hydrochloride

Off-White Solid

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

Rac Viloxazine Hydrochloride is research useful chemical used as an antidepressant.

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.

Psychotropic

Viloxazine (ICI 58,834) is an orally active serotonin norepinephrine modulating agent (SNMA) originally reported as a norepinephrine reuptake inhibitor (NRI) with antidepressant (ED10 from 0.3-1 mg/kg p.o. against reserpine-induced hypothermia in mice), while exhibiting less sedative efficacy (locomotor activity reduction ED10 from 3-10 mg/kg p.o. in mice) and no monoamine oxidase inhibitory potency. Viloxazine shows 5-HT2B antagonist and 5-HT2C agonist activity in vitro and increases extracellular 5-HT levels in the prefrontal cortex (PFC) in vivo, a brain area implicated in Attention deficit hyperactivity disorder (ADHD).