81447-78-1

Basic information

• Product Name: Levlofexidine
• Synonyms: Levlofexidine;(R)-Lofexidine;2-[(1R)-1-(2,6-Dichlorophenoxy)ethyl]-4,5-dihydro-1H-imidazole;(-)-2-[(R)-1-(2,6-Dichlorophenoxy)ethyl]-2-imidazoline;2-[(1R)-1-(2,6-Dichlorophenoxy)ethyl]-4,5-dihydro-
• CAS NO: 81447-78-1
• Molecular Formula: C₁₁H₁₂Cl₂N₂O
• Molecular Weight: 259.135
• Product Categories: Aromatics;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 81447-78-1.mol
• Article Data: 12

Chemical Properties

• Boiling Point: 421.5°Cat760mmHg
• Flash Point: 208.7°C
• Appearance: /
• Density: 1.39g/cm³
• Vapor Pressure: 6.35E-07mmHg at 25°C
• Refractive Index: 1.61
• CAS DataBase Reference: Levlofexidine(CAS DataBase Reference)
• NIST Chemistry Reference: Levlofexidine(81447-78-1)
• EPA Substance Registry System: Levlofexidine(81447-78-1)

Safety Data

• Hazardous Substances Data: 81447-78-1(Hazardous Substances Data)

Usage

Uses

Levlofexidine is the R-enantiomer of Lofexidine,it is a α2-Adrenoceptor agonist related structurally to Clonidine, Used in treatment of opioid withdrawal symptoms; antihypertensive.

InChI:InChI=1/C11H12Cl2N2O/c1-7(11-14-5-6-15-11)16-10-8(12)3-2-4-9(10)13/h2-4,7H,5-6H2,1H3,(H,14,15)/t7-/m1/s1

Upstream product

• 78302-27-9 2-(2,6-dichlorophenoxy)-propionitrile 
• 107-15-3 ethylenediamine 
• 87-65-0 2,6-Dichlorophenol 
• 1112401-07-6 C₁₀H₁₀Cl₂O₃ 
• 344559-34-8 (±)ethyl 2-(2,6-dichlorophenoxy)propionate 
• 101934-14-9 1,3-Dichloro-2-((R)-2,2,2-triethoxy-1-methyl-ethoxy)-benzene 
• 73372-53-9 lofexidine 
• 86981-81-9 (-)-2-(2,6-dichlorophenoxy)propionitrile 
• 87789-42-2 (R)-(-)-2-(2,6-dichlorophenoxy)propionamide 
• 383898-16-6 (-)-ethyl 2-(2,6-dichlorophenoxy)propionate 
• 101934-13-8 (R)-2-(2,6-Dichloro-phenoxy)-propionimidic acid ethyl ester; hydrochloride 

Downstream Products

• 81447-79-2 (+)-Lofexidine 
• 87038-06-0 (-)-Lofexidine hydrochloride 
• 21498-08-8 lofexidine hydrochloride 

Relevant articles and documents

An Easy, Convenient, and Safe Process for the Synthesis of Lofexidine Hydrochloride

A very efficient, cost-effective, and easily scalable process for the synthesis of lofexidine hydrochloride (1), an alpha 2-adrenergic receptor agonist used for treating opioid withdrawal is presented. Process development allows the preparation of lofexidine hydrochloride (1) through a one-pot amidation/imidazoline ring formation reaction, starting from ethyl 2-(2,6-dichlorophenoxy)propionate (13) and ethylenediamine (5) by the action of titanium isopropoxide. The required intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (13) can efficiently be obtained through O-alkylation of 2,6-dichlorophenol (2) with ethyl 2-chloropropionate (12) using potassium carbonate as an acid-scavenger agent.

A PROCESS FOR THE SYNTHESIS OF LOFEXIDINE

Disclosed is a process for the synthesis of lofexidine of formula (I) and the hydrochloride salt thereof (II), from ethyl 2-(2,6-dichlorophenoxy)propionate (III) and ethylenediamine in the presence of tetravalent titanium alkoxides, preferably titanium isopropoxide, in an apolar solvent such as toluene. A further object of the present invention is a process for the preparation of the intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (III) from 2,6-dichlorophenol and ethyl 2-chloropropionate in the presence of a polar aprotic solvent and an alkali or alkaline earth carbonate salt, preferably potassium carbonate. Both processes are more cost-effective and more easily industrially scalable than the known procedures, thus enabling the active ingredient to be obtained with high yields at a limited cost.

ENANTIOSELECTIVE SYNTHESIS OF (+) AND (-)-2-[1-(2,6-DICHLOROPHENOXY)-ETHYL]-1,3-DIAZACYCLOPENT-2-3ENE

This application provides a method for the enantioselective synthesis of (+) and (?) lofexidine or 2-[1-(2,6)-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene.