22801-44-1

Basic information

• Product Name: Mepivacaine
• Synonyms: MEPIVACAINE;N-(2,6-Dimethylphenyl)-1-Piperidinecarboxamide;N-(2,6-Dimethylphenyl)-1-methylpiperidine-2-carboxamide;MepivacaineBase;Mepivacaine HCl (base);Mepivacaine N-(2,6-Dimethylphenyl)-1-methylpiperidine-2-carboxamide;Mepivacaine(Cas number22801-44-1)
• CAS NO: 22801-44-1
• Molecular Formula: C15H22N2O
• Molecular Weight: 246.35
• EINECS: 1312995-182-4
• Mol File: 22801-44-1.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 383.1 °C at 760 mmHg
• Flash Point: 185.5 °C
• Appearance: /
• Density: 1.077 g/cm³
• Vapor Pressure: 4.52E-06mmHg at 25°C
• Refractive Index: 1.567
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), DMSO (Slightly), Ethanol (Slightly), Methanol (Slightly)
• PKA: pKa 7.73(H2O,t =25±0.2,I=0.01(NaCl)) (Uncertain)
• CAS DataBase Reference: Mepivacaine(CAS DataBase Reference)
• NIST Chemistry Reference: Mepivacaine(22801-44-1)
• EPA Substance Registry System: Mepivacaine(22801-44-1)

Safety Data

• Hazardous Substances Data: 22801-44-1(Hazardous Substances Data)

Usage

Description

Mepivacaine, a synthetic local anesthetic of the amide type, is structurally related to lidocaine. It is used for its numbing effect on nerve tissues, providing pain relief during various medical procedures. Mepivacaine is known for its rapid onset and is metabolized in the liver, with metabolites excreted through bile and urine.
Used in Pharmaceutical Industry:
Mepivacaine is used as a local anesthetic for various medical procedures, including infiltration anesthesia, dental procedures, peripheral nerve block, and epidural block. It is available in solutions ranging from 1% to 3% and provides rapid onset of anesthesia, typically between 3 to 20 minutes for sensory block.
Used in Biological Research:
In the field of biological research, Mepivacaine is utilized in studies involving 2-adamantanamine, where it has been observed to produce prolonged spinal block in rats. This application aids in understanding the effects and potential uses of related compounds in medical and pharmaceutical settings.

Originator

Carboraine,Winthrop,US,1960

Manufacturing Process

Ethyl magnesium bromide is prepared in the usual way by reacting 185 parts by weight of ethyl bromide in 800 parts of anhydrous ether with 37 parts by weight of magnesium turnings. Under vigorous stirring 121 parts of 2,6- dimethyl aniline are added at a rate depending on the vigor of the gas evaporation. When the evolution of gas has ceased, 85 parts by weight of Nmethylpipecolic acid ethyl ester are added to the 2,6-dimethyl aniline magnesium bromide slurry. The mixture is refluxed for ? hour with continued stirring, after which it is cooled down. Dilute hydrochloric acid is added carefully in order to dissolve and hydrolyze the magnesium compound formed. The pH is adjusted to 5.5 and the water phase separated and extracted with additional ether in order to remove the surplus dimethyl aniline. After addition of an excess of ammonia to the solution, the reaction product, Nmethylpipecolic acid 2,6-dimethyl anilide, is recovered by extraction with isoamyl alcohol. The isoamyl alcohol solution is evaporated to dryness, the product dissolved in dilute hydrochloric acid, treated with charcoal and reprecipitated with NaOH. N-methylpipecolic acid 2,6-dimethyl anilide is obtained in crystalline form.

Therapeutic Function

Local anesthetic

Clinical Use

Mepivacaine hydrochloride [N-(2, 6-dimethylphenyl)-1-methyl 2-piperidinecarboxamide monohydrochloride] is an amino amide-type local anesthetic agent widely used to provide regional analgesia and anesthesia by local infiltration, peripheral nerve block, and epidural and caudal blocks. The pharmacological and toxicological profile of mepivacaine is quite similar to that of lidocaine, except that mepivacaine has a slightly longer duration of action and lacks the vasodilator activity of lidocaine. For this reason, it serves as an alternate choice for lidocaine when addition of epinephrine is not recommended in patients with hypertensive vascular disease.

Synthesis

Mepivacaine is N-(2,6-dimethylphenyl)-1-methyl-2-piperindincarboxamide (2.2.3). Two primary methods of synthesis have been suggested. According to the first, mepivacaine is synthesized by reacting the ethyl ester of 1-methylpiperindine-2-carboxylic acid with 2,6-dimethylanilinomagnesium bromide, which is synthesized from 2,6- dimethylaniline and ethylmagnesium bromide [12–14]. According to the figure below, reacting 2,6-dimethylaniline with the acid chloride of pyridine-carboxylic acid first gives the 2,6-xylidide of α-picolinic acid (2.2.4). Then the aromatic pyridine ring is reduced to piperidine by hydrogen in the presence of a platinum on carbon catalyst. The resulting 2,6-xylidide α-pipecolinic acid (2.2.5) is methylated to mepivacaine using formaldehyde with simultaneous reduction by hydrogen in the presence of platinum on carbon catalyst [15].

Metabolism

Mepivacaine undergoes extensive hepatic metabolism catalyzed by CYP1A2, with only a small percentage of the administered dosage (<10%) being excreted unchanged in the urine. The major metabolic biotransformations of mepivacaine are N-dealkylation (to give the N-demethylated compound 2′,6′-pipecoloxylidide) and aromatic hydroxylations. These metabolites are excreted as their corresponding glucuronides.

InChI:InChI=1/C15H22N2O/c1-11-7-6-8-12(2)14(11)16-15(18)13-9-4-5-10-17(13)3/h6-8,13H,4-5,9-10H2,1-3H3,(H,16,18)

Upstream product

• 111562-44-8 2-(2,6-dimethyl-phenylcarbamoyl)-1-methyl-pyridinium; iodide 
• 77-78-1 dimethyl sulfate 
• 626-67-5 N-methylcyclohexylamine 
• 40397-98-6 2,5-dimethylphenyl isocyanate 
• 98-98-6 2-Picolinic acid 
• 39627-98-0 2-pyridine-carboxamide-N-(2,6-dimethylphenyl) 
• 67-56-1 methanol 
• 87-62-7 2,6-dimethylaniline 
• 50-00-0 formaldehyd 
• 27262-40-4 (S)-2',6'-pipecoloxylidide 
• 74-88-4 methyl iodide 
• 98626-58-5 L-pipecolic acid chloride hydrochloride 
• 3105-95-1 pipecolinic acid 

Relevant articles and documents

A convenient and highly enantioselective synthesis of (S)-2-pipecolic acid: an efficient access to caine anesthetics

A novel and enantioselective synthesis of (S)-2-pipecolic acid (5) has been achieved from Oppolzer’s sultam (1) and ethyl N-(diphenylmethylene)glycinate (2) as readily available starting materials. The highly stereoselective alkylation of chiral glycine intermediate (3) with 1,4-dibromobutane afforded the key backbone of (S)-2-pipecolic acid (5) in one-step that was utilized into the preparation of the local anesthetics mepivacaine, ropivacaine and bupivacaine.

PROCESS FOR THE PREPARATION OF (S)-1-ALKYL-2',6'-PIPECOLOXYLIDIDE COMPOUND

The present invention relates to an improved process for the preparation of high chiral purity (S)-1-alkyl-2',6'-Pipecoloxylidide compound such as Ropivacaine, Levobupivacaine or salts thereof, which comprises crystallization of (S)-1-alkyl-2',6'- Pipecoloxylidide acid addition salt in a non-alcoholic and non-ketonic solvent.

Radical fixation of functionalized carbon resources: α-sp 3C - H carbamoylation of tertiary amines with aryl isocyanates

A new carbamoylation of tertiary amines is reported. This rare C - H transformation features the direct generation of α-aminoalkyl radicals from tertiary amines, followed by the addition of the resultant nucleophilic radicals to isocyanates, enabling unique access to N,N-dialkylated amino acid derivatives. The authors put forward a mechanistic proposal that is based on the isolation of borinamides produced by capturing nitrogen radical intermediates with Et3B. The present transformation provides a novel one-step process for producing mepivacaine, a clinically important local anesthetic, from readily available materials.