![](/CAS/GIF/21498-08-8.gif)
Lofexidine hydrochloride synthesis
- Product Name:Lofexidine hydrochloride
- CAS Number:21498-08-8
- Molecular formula:C11H13Cl3N2O
- Molecular Weight:295.59
![Propanoic acid, 2-(2,6-dichlorophenoxy)-, ethyl ester, (-)-](/CAS/20210305/GIF/86981-78-4.gif)
86981-78-4
0 suppliers
inquiry
![Ethylenediamine](/CAS/GIF/107-15-3.gif)
107-15-3
9 suppliers
$11.19/25ML
![Lofexidine hydrochloride](/CAS/GIF/21498-08-8.gif)
21498-08-8
131 suppliers
$35.00/250mg
Yield:21498-08-8 66.9%
Reaction Conditions:
Stage #1: (±)ethyl 2-(2,6-dichlorophenoxy)propionate;ethylenediaminewith aluminum isopropoxide in toluene at 10 - 105;Inert atmosphere;
Stage #2: with hydrogenchloride in isopropyl alcohol at 10 - 50; for 2.5 h;Solvent;Temperature;
Steps:
5 Example 5: Preparation of 2-(1-(2,6-dichlorophenoxy)ethyl)-4,5-dihydro-1H- imidazole monohydrochloride (Lofexidine hydrochloride) (compound 1-HCI)
A solution of 20 g of ethyl 2-(2,6-dichlorophenoxy)propanoate in 80 mL of toluene was added to a solution of 31.1 g of aluminium isopropoxide and 9.1 g of ethylenediamine in 220 mL of toluene at 20-25 °C while stirring under nitrogen atmosphere. The resulting mixture was heated up to 105 °C and stirred at this temperature until the reaction was completed. The mixture was cooled down to 10-15 °C. Then, 10 g of celite and 32 mL of isopropanol were added, followed by the dropwise addition of 100 mL of deionised water at 10-15 °C. The resulting mixture was stirred for 1 hour at 20-25 °C and the resulting solid was filtered. The filtered solution was allowed to settle and a biphasic mixture was obtained. Then, the aqueous layer was removed and the resulting organic layer was washed with 60 ml_ of deionised water. After heating the resulting organic solution up to 45-50 °C, a solution of 3.0 g of hydrogen chloride gas in 19.6 ml_ of isopropanol was added dropwise and the resulting mixture was stirred for a minimum of 30 minutes at this temperature. The resulting suspension was stirred for 1 hour at 20-25 °C followed by 1 hour at 10-15 °C. The precipitated solid was filtered and washed with toluene to obtain a wet solid. Yield: 66.9%. Purity (HPLC): 99.28%.
References:
WO2021/209617,2021,A1 Location in patent:Page/Page column 15-16
![2,6-Dichlorophenol](/CAS/GIF/87-65-0.gif)
87-65-0
399 suppliers
$10.00/10g
![Lofexidine hydrochloride](/CAS/GIF/21498-08-8.gif)
21498-08-8
131 suppliers
$35.00/250mg
![Propanenitrile, 2-(2,6-dichlorophenoxy)-, (+)-](/CAS/20210305/GIF/87789-43-3.gif)
87789-43-3
0 suppliers
inquiry
![Ethylenediamine](/CAS/GIF/107-15-3.gif)
107-15-3
9 suppliers
$11.19/25ML
![Lofexidine hydrochloride](/CAS/GIF/21498-08-8.gif)
21498-08-8
131 suppliers
$35.00/250mg