130018-87-0

Basic information

• Product Name: Levocetirizine dihydrochloride
• Synonyms: LEVOCETIRIZINE 2HCL;LEVOCETIRIZINE DIHCL;LEVOCETIRIZINE DIHYDROCHLORIDE;LEVOCETIRIZINE HCL;LEVOCETRIZINE DIHYDROCHLORIDE;[2-[4-[(r)-(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]-acetic acid dihydrochloride;LevocetrizineHCl;LEVOCITIRIZINE DIHYDROCHLORIDE
• CAS NO: 130018-87-0
• Molecular Formula: C21H27Cl3N2O3
• Molecular Weight: 461.81
• EINECS: 200-659-6
• Product Categories: API's;Levocetirizine;Histamine receptor;API;Levocitirizine 2HCl;Antibiotics
• Mol File: 130018-87-0.mol

Chemical Properties

• Melting Point: 215-220°C
• Boiling Point: 542.1 °C at 760 mmHg
• Flash Point: 281.6 °C
• Appearance: white or off-white crystalline powder
• Storage Temp.: room temp
• Solubility: H2O: ≥23mg/mL
• Merck: 14,2022
• CAS DataBase Reference: Levocetirizine dihydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Levocetirizine dihydrochloride(130018-87-0)
• EPA Substance Registry System: Levocetirizine dihydrochloride(130018-87-0)

Safety Data

• Hazard Codes: Xn,N
• Statements: 22-50/53
• Safety Statements: 60-61
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• RTECS: AG0990000
• Hazardous Substances Data: 130018-87-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Levocetirizine dihydrochloride is used as an antihistamine for the relief of symptoms associated with allergic rhinitis (both seasonal and perennial) in adults and children aged 6 years and older. It is also used for the treatment of uncomplicated skin manifestations of chronic idiopathic urticaria in the same age group.
Used in Analytical Chemistry:
Levocetirizine dihydrochloride has been utilized as a standard in the optimization of thin layer chromatography and in the preparation of racemic cetirizine standard for subcritical fluid chromatography-tandem mass spectrometry analysis. This application aids in the development and refinement of analytical techniques for drug testing and quality control.

Biochem/physiol Actions

Levocetirizine hydrochloride is a nonsedating antihistamine. It is a histamine H1-receptor antagonist, the active isomer of cetirizine. Levocetirizine has high bioavailability, high affinity for and occupancy of the H1 receptor.

InChI:InChI=1/C21H25ClN2O2.ClH/c22-19-10-8-18(9-11-19)21(17-5-2-1-3-6-17)24-15-13-23(14-16-24)12-4-7-20(25)26;/h1-3,5-6,8-11,21H,4,7,12-16H2,(H,25,26);1H/t21-;/m0./s1

Upstream product

• 181119-59-5 (2-{4-[(S)-(4-Chloro-phenyl)-phenyl-methyl]-piperazin-1-yl}-ethoxy)-acetic acid butyl ester 
• 7647-01-0 hydrogenchloride 
• 130018-77-8 levocetirizine 
• 246870-46-2 (S)-(-)-cetirizine ethyl ester 
• 104-88-1 4-chlorobenzaldehyde 
• 100-52-7 benzaldehyde 
• 186249-76-3 (R,E)-2-methyl-N-(phenylmethylene)-2-propanesulfinamide 
• 163837-32-9 (S)-4-chloro-α-phenyl-benzenemethanamine 
• 336105-23-8 (R)-(-)-N-[(1E)-(4-chlorophenyl)methylene]-2-methyl-2-propanesulfinamide 
• 439695-63-3 (R_S,S)-(1-(4-chlorophenyl)-1-phenylmethyl)-2-methylpropanesulfinamide 
• 439858-21-6 1-[(S)-(4-chlorophenyl)(phenyl)methyl]piperazine 
• 163837-58-9 1-[(S)-(4-Chloro-phenyl)-phenyl-methyl]-4-(toluene-4-sulfonyl)-piperazine 
• 181119-50-6 (2-Piperazin-1-yl-ethoxy)-acetic acid butyl ester 
• 181119-68-6 4-(2-Butoxycarbonylmethoxy-ethyl)-piperazine-1-carboxylic acid benzyl ester 

Relevant articles and documents

A novel synthesis of the enantiomers of an antihistamine drug by piperazine formation from a primary amine

An enantioselective synthesis of each enantiomer of the antihistamine drug 2-(2-{4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl}ethoxy)acetic acid dihydrochloride (1) is described, involving the preparation of the benzhydrylpiperazine portion of the molecule from reaction of each enantiomer of 4-chlorobenzhydrylamine with N,N-bis(2-chloroethyl)-4-methylbenzenesulfonamide. A modification of standard toluenesulfonamide deprotection with hydrogen bromide in acetic acid was introduced, substituting 4-hydroxybenzoic acid for phenol.

A synthesis process of cetirizine hydrochloride

A new technology for synthesizing cetirizine hydrochloride. The technology includes following steps: oxidizing hydroxyzine, which is used as a raw material, into a substance containing an aldehyde group; further oxidizing the substance containing the aldehyde group into cetirizine; and finally performing a salification and purification process to obtain the cetirizine hydrochloride. A total yield of the synthetic method is higher than 80%. Meanwhile, the method is simple in operation, is short in production period, is low in energy consumption and cost, is little in waste water, waste gas and residues and is suitable for large-scale industrial production.

New manufacturing procedure of cetirizine

A new procedure for the manufacture of cetirizine dihydrochloride via the new intermediate 2-(2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)- N,N-dimethylacetamide dihydrochloride, synthesized by O-alkylation of 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethanol with 2-chloro-N,N-dimethylacetamide, is elaborated. Hydrolysis of the resulting amide and subsequent salification provided cetirizine dihydrochloride.

AN IMPROVED PROCESS FOR THE PREPARATION OF ANTIHISTAMINIC DRUGS VIA A NOVEL CARBAMATE INTERMEDIATE

The present invention relates to a novel racemic or optically active carbamate intermediate of formula (IV A). This novel racemic or optically active carbamate intermediate of formula (IV A) can be used to prepare drugs having antihistaminic activity such as cetirizine (IA), meclizine (IB), chlorcyclizine (IC), clocinizine (ID), buclizine (IE) and enantiomers thereof such as levocetirizine (I). Further, disclosed herein is an improved process for the preparation of levocetirizine via a novel optically active intermediate i.e. compound of formula (IV). Also, disclosed herein is a novel process for the preparation of compound (II) and for crystallization of its salt.

Processes for the Synthesis of Levocetirizine and Intermediates for Use Therein

The present invention provides a compound of formula (IV) wherein R is Cl, Br, NO2, OH or OR′, and R′ is alkyl, and its use in the synthesis of levocetirizine, including its use in the synthesis of (?)-1-[(4-chlorophenyl)-phenylmethyl]piperazin

Process for obtaining cetirizine dihydrochloride

Process for the synthesis of cetirizine dihydrochloride, wherein (a) a solution of {2-[4-(α-phenyl-p-chlorobenzyl)piperazin-1-yl]}ethanol in 1-7 volumes, referred to the weight of {2-[4-(α-phenyl-p-chlorobenzyl)piperazin-1-yl]}ethanol, of an organic solvent having a boiling point higher than 90° C. and being chosen from the group consisting of aliphatic, cycloalifatic or aromatic solvents is provided, whereafter(b) per equivalent of {2-[4-(α-phenyl-p-chlorobenzyl)piperazin-1-yl]}ethanol employed, 1-2 equivalents of a metal haloacetate or of haloacetic acid, as well as 3-7 equivalents of an alkaly metal hydroxyde are added to the solution as per (a), providing a reaction mixture, where 0.05-0.3 volumes, referred to the weight of {2-[4-(α-phenyl-p-chlorobenzyl)piperazin-1-yl]}ethanol employed, of water and 0.1-1.2 volumes, referred to the weight of {2-[4-(α-phenyl-p-chlorobenzyl)piperazin-1-yl]}ethanol employed, of a polar aprotic, water miscible solvent are added, keeping the internal temperature of the reaction mixture below 60° C., whereafter(c) the cetirizine base formed within the reaction mixture is converted into its dihydrochloride salt and isolated as such.

PROCESSES FOR THE SYNTHESIS OF LEVOCETIRIZINE AND INTERMEDIATES FOR USE THEREIN

The present invention provides a compound of formula (IV) wherein R is Cl, Br, NO2, OH or OR', and R' is alkyl, and its use in the synthesis of levocetirizine, including its use in the synthesis of (-)-1-[(4-chlorophenyl)-phenyl methyl] piperaz

PROCESS FOR PREPARATION OF SUBSTANTIALLY OPTICALLY PURE LEVOROTATORY AND DEXTROROTATORY ENANTIOMERS OF CETIRIZINE USING NOVEL INTERMEDIATES

The present invention relates to a novel and commercially viable process for substantially optically pure levorotatory and dextrorotatory enantiomers of cetirizine intermediate, 1-[(4-chlorophenyl)phenylmethyl]piperazine, thereby producing substantially optically pure levorotatory and dextrorotatory enantiomers of cetirizine and their pharmaceutical acceptable acid addition salts thereof in high purity and in high yield using novel intermediates.

NEW PROCESS FOR THE PREPARATION OF LEVOCETIRIZINE AND INTERMEDIATES THEREOF

The present invention describes a novel process for the preparation of levocetirizine and pharmaceutically acceptable acid addition salts thereof via a ketocetirizine ester and new ketocetirizine ester intermediates used in that process. reaction of ketocetirizine of the formula (IIIb) to a ketocetirizine ester of the formula (IV) or a salt thereof.

A PROCESS FOR THE SYNTHESIS OF 2-[2-[4-[(4-CHLOROPHENYL)PHENYL METHYL]-1-PIPERAZINYL] ETHOXY ACETIC ACID

TAbstract A process for the preparation of 2-[2-[4-[(4-chloro phenyl) phenyl methyl]-1-piperazinyl] ethoxy acetic acid of formula (Ia) and pharmaceutically acceptable salts thereof, and compounds of formula (IIa) and (VIIIa), wherein R1 = H or C1-C4 alkyl; R2 = aryl or heteroaryl or R1 and R2 together with the carbon to which they are attached form a C3-C8 cycloalkyl group and X is a suitable leaving group for example, chlorine, bromine, iodine, 4-methylphenyl-sulfonyloxy, methylsulfonyloxy group or 4-bromophenyl-sulfonyloxy group are described.