84057-95-4

Basic information

• Product Name: Ropivacaine
• Synonyms: ROPIVACAINE MESYLATER;RopivacaineHcl/MesylateBase;ROPACARAINEHCL;(S)-N-(2，6-Dimethylphenyl)-1-pKIpyl-2-piperidinecarboxamide;Naropin;2-Piperidinecarboxamide, N-(2,6-dimethylphenyl)-1-propyl-, (2S)-;Naropine;(2S)-1-Propyl-2-(2,6-dimethylphenyl)carbamoylpiperidine
• CAS NO: 84057-95-4
• Molecular Formula: C₁₇H₂₆N₂O
• Molecular Weight: 274.4
• Product Categories: API
• Mol File: 84057-95-4.mol

Chemical Properties

• Melting Point: 144-146°
• Boiling Point: 410.2 °C at 760 mmHg
• Flash Point: 201.9 °C
• Appearance: /
• Density: 1.044 g/cm³
• Storage Temp.: Refrigerator
• Solubility: Aqueous Acid (Slightly), Chloroform (Slightly), DMSO (Slightly), Methanol (Sligh
• PKA: 8.16(at 25℃)
• CAS DataBase Reference: Ropivacaine(CAS DataBase Reference)
• NIST Chemistry Reference: Ropivacaine(84057-95-4)
• EPA Substance Registry System: Ropivacaine(84057-95-4)

Safety Data

• Hazardous Substances Data: 84057-95-4(Hazardous Substances Data)

Usage

Uses

Used in Medical Procedures:
Ropivacaine is used as a local anesthetic for medical procedures, providing anesthesia during surgeries or C-sections, and easing labor pains. It is frequently used in epidural procedures as labor analgesia.
Used in Pharmaceutical Industry:
Ropivacaine HCl is an anaesthetic agent that is used in the pharmaceutical industry for the development of anesthetic medications. It is the first compound in its family to be produced as the pure (S)-enantiomer, which has less cardiotoxicity compared to the (R)-enantiomer.
Used in Pain Management:
Ropivacaine is used as a local (in only one area) anesthesia for a spinal block, also called an epidural. It blocks the nerve impulses that send pain signals to the brain, providing pain relief during medical procedures.
Used in Cardiovascular Safety:
Due to its reduced lipophilicity and stereoselective properties, ropivacaine has significantly reduced CVS toxicity compared to bupivacaine, making it a safer option for patients with cardiovascular concerns.
Used in Peripheral Vasculature:
Ropivacaine has a diphasic effect on peripheral vasculature, being vasoconstrictive when injected at a concentration below 0.5 w/v% and causing dilation at concentrations over 1 w/v%. This property can be useful in specific medical applications where control of blood flow is necessary.

Biological Functions

Ropivacaine (Naropin) is a recently developed longacting amide-linked local anesthetic. Its duration of action is similar to that of bupivacaine, but it is slightly less potent and requires higher concentrations to achieve the same degree of block. Its primary advantage over bupivacaine is its lesser degree of cardiotoxicity.

Mechanism of action

Ropivacaine is a member of the amino amide class of local anesthetics and is supplied as the pure S-(- )-enantiomer. Local anesthetics block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone.

Pharmacology

This is a single (S–) enantiomer, similar in structure to bupivacaine. S ubstitution of a propyl for the butyl side chain of bupivacaine reduces lipid solubility; this leads to reduced potential for toxicity and also greater separation between sensory and motor blockade. Efficacy is similar, but motor block is reduced compared with equianalgesic doses of racemic bupivacaine.

Clinical Use

Ropivacaine is a long-acting amide-type local anestheticwith inherent vasoconstrictor activities, so it does not requirethe use of additional vasoconstrictors. It is approved forepidural, nerve block, infiltration, and intrathecal anesthesia.

Side effects

Reactions to ropivacaine are characteristic of those associated with other amide-type local anesthetics. A major cause of adverse reactions to this group of drugs may be associated with excessive plasma levels, which may be due to overdosage, unintentional intravascular injection or slow metabolic degradation.Check with your doctor or nurse immediately if any of the following side effects occur:More commonBlurred visionchest pain or discomfortconfusiondizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting positionlightheadedness, dizziness, or faintingslow or irregular heartbeatsweatingunusual tiredness or weaknessLess commonBurning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelingschillsdecrease in frequency or amount of urinedifficulty in passing urine (dribbling)feverpainful urinationRareAbsence of or decrease in body movementagitationanxietyhttps://www.mayoclinic.org/drugs-supplements/ropivacaine-injection-route/side-effects/drg-20065875https://www.accessdata.fda.gov/

Metabolism

The metabolism of ropivacaine in human is mediated by hepatic CYP1A2 isozymes and, to a minor extent, by CYP3A4. The major metabolite is 3-hydroxyropivacaine, and the minor metabolite is (S)-2′,6′-pipecoloxylidide (a N-dealkylated product).Ropivacaine is extensively metabolized in the liver, predominantly by aromatic hydroxylation mediated by cytochrome P4501A to 3-hydroxyropivacaine. After a single IV dose approximately 37% of the total dose is excreted in the urine as both free and conjugated 3-hydroxy ropivacaine. Low concentrations of 3-hydroxy ropivacaine have been found in the plasma. Urinary excretion of the 4-hydroxy ropivacaine, and both the 3-hydroxy N-de-alkylated (3-OH-PPX) and 4-hydroxy N-dealkylated (4-OH-PPX) metabolites account for less than 3% of the dose. An additional metabolite, 2- hydroxy-methyl-ropivacaine, has been identified but not quantified in the urine. The N-de-alkylated metabolite of ropivacaine (PPX) and 3-OH-ropivacaine are the major metabolites excreted in the urine during epidural infusion. Total PPX concentration in the plasma was about half as that of total ropivacaine; however, mean unbound concentrations of PPX were about 7 to 9 times higher than that of unbound ropivacaine following continuous epidural infusion up to 72 hours. Unbound PPX, 3- hydroxy and 4-hydroxy ropivacaine, have a pharmacological activity in animal models less than that of ropivacaine. There is no evidence of in vivo racemization in urine of ropivacaine.https://www.accessdata.fda.gov

InChI:InChI=1/C17H26N2O.CH4O3S/c1-4-11-19-12-6-5-10-15(19)17(20)18-16-13(2)8-7-9-14(16)3;1-5(2,3)4/h7-9,15H,4-6,10-12H2,1-3H3,(H,18,20);1H3,(H,2,3,4)

Upstream product

• 98626-61-0 1-propyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide 
• 106-94-5 propyl bromide 
• 27262-40-4 (S)-2',6'-pipecoloxylidide 
• 123-38-6 propionaldehyde 
• 26250-84-0 (S)-(-)-1-(tert-butoxycarbonyl)-2-piperidinecarboxylic acid 
• 3105-95-1 pipecolinic acid 
• 98626-58-5 L-pipecolic acid chloride hydrochloride 
• 926275-68-5 (S)-1-propylpiperidine-2-carboxylic acid 
• 87-62-7 2,6-dimethylaniline 
• 98717-15-8 ropivacaine hydrochloride 
• 33420-15-4 n-propyl 4-nitrobenzenesulfonate 

Downstream Products

• 98717-15-8 ropivacaine hydrochloride 
• 132112-35-7 ropivacaine hydrochloride monohydrate 
• 98626-61-0 1-propyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide 

Relevant articles and documents

Determination of the enantiomeric purity of S-ropivacaine by capillary electrophoresis with methyl-β-cyclodextrin as chiral selector using conventional and complete filling techniques

Capillary electrophoresis (CE) methods based on the conventional and complete filling techniques for determination of the enantiomeric purity of S-ropivacaine are described. The complete filling technique is a separation method which can be used instead of the partial filling technique in order to reduce the total analysis time, when the chiral selector solution does not absorb UV light. In the complete filling technique the total length of the capillary is filled with the chiral selector solution, prior to application of the analyte. During the run both ends of the capillary are connected to the background electrolyte, i.e. without chiral agent. An interlaboratory study was performed to validate the method. The limit of detection and quantification for R-ropivacaine were found to be about 0.6 and 1.6 μg/ml, respectively, corresponding to 0.1 and 0.25% enantiomeric purity of S-ropivacaine. Good performances were demonstrated for the repeatability and linearity. The consumption of the chiral selector was about 160 times lower with the complete filling technique compared with the conventional CE technique. Copyright (C) 1999 Elsevier Science B.V.

Method for preparing ropivacaine hydrochloride

The preparation method comprises the following specific steps: 1) reacting (S)- piperidine -2 - formic acid with propionaldehyde in the presence of a reducing agent and an aprotic solvent to obtain the intermediate 1. 2). N. NIn the presence of -dimethylformamide and an aprotic solvent, the intermediate 1 obtained in step 1) and the acylating agent are subjected to an acylation reaction to give an intermediate 2. 3). N. N[-] The intermediate 2 obtained in step 2) and 2 and 6 -dimethylaniline are subjected to a condensation reaction in the presence of dimethylformamide and basic conditions to give an intermediate 3. 4) The intermediate 3 obtained in step 3) is salified with hydrochloric acid to give the ropivacaine hydrochloride crude product. 5) The ropivacaine hydrochloride is purified to obtain ropivacaine hydrochloride. The method has the advantages that the product purity is higher than 99.99%, the synthesis process is mild in reaction condition, simple in preparation process, low in cost, safe and environment-friendly, and is suitable for industrial production.

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.

Preparation method of ropivacaine hydrochloride

The invention discloses a preparation method of ropivacaine hydrochloride. The preparation method comprises steps as follows: (1) preparation of an intermediate (I), (2) preparation of an intermediate (II), (3) preparation of a crude product and (4) refin

Effect of Partially Fluorinated N-Alkyl-Substituted Piperidine-2-carboxamides on Pharmacologically Relevant Properties

The modulation of pharmacologically relevant properties of N-alkyl-piperidine-2-carboxamides was studied by selective introduction of 1–3 fluorine atoms into the n-propyl and n-butyl side chains of the local anesthetics ropivacaine and levobupivacaine. The basicity modulation by nearby fluorine substituents is essentially additive and exhibits an exponential attenuation as a function of topological distance between fluorine and the basic center. The intrinsic lipophilicity of the neutral piperidine derivatives displays the characteristic response noted for partially fluorinated alkyl groups attached to neutral heteroaryl systems. However, basicity decrease by nearby fluorine substituents affects lipophilicities at neutral pH, so that all partially fluorinated derivatives are of similar or higher lipophilicity than their non-fluorinated parents. Aqueous solubilities were found to correlate inversely with lipophilicity with a significant contribution from crystal packing energies, as indicated by variations in melting point temperatures. All fluorinated derivatives were found to be somewhat more readily oxidized in human liver microsomes, the rates of degradation correlating with increasing lipophilicity. Because the piperidine-2-carboxamide core is chiral, pairs with enantiomeric N-alkyl groups are diastereomeric. While little response to such stereoisomerism was observed for basicity or lipophilicity, more pronounced variations were observed for melting point temperatures and oxidative degradation.

A Survey of the Borrowing Hydrogen Approach to the Synthesis of some Pharmaceutically Relevant Intermediates

The use of the "borrowing hydrogen strategy" in the synthesis of a number of typical pharmaceutical intermediates has been investigated. The main aim of this work was to investigate the scope and limitations of current methodology using standard laboratory techniques in an industrial context. Some interesting and significant results were achieved across a diverse set of complex substrates; however several drawbacks with this approach were identified, such as the high loading, poor turnover, and susceptibility to substrate inactivation of the catalysts. These are areas which are highlighted for future investigation and improvements.

PROCESS FOR PRODUCING OPTICALLY ACTIVE N-ALKYL-PIPERIDINE-2-CARBOXANILIDE

Disclosed herein is a process for producing optically active 1-n-propyl-2',6'-dimethyl-2-piperidinecarboxanilide. The process comprises of reacting n-propyl pipecolate ester with 2,6-dimethylanilino magnesium halide. The 1-n-propyl-2',6'-dimethyl-2-piperi

Highly enantioselective catalytic dynamic resolution of N-boc-2-lithiopiperidine: Synthesis of (R)-(+)- N-boc-pipecolic acid, (S)-(-)-coniine, (S)-(+)-pelletierine, (+)-β-conhydrine, and (S)-(-)-ropivacaine and formal synthesis of (-)-lasubine II and (+)-cermizine C

The catalytic dynamic resolution (CDR) of rac-2-lithio-N-Boc-piperidine using chiral ligand 8 or its diastereomer 9 in the presence of TMEDA has led to the highly enantioselective syntheses of both enantiomers of 2-substituted piperidines using a wide range of electrophiles. The CDR has been applied to the synthesis of (R)- and (S)-pipecolic acid derivatives, (+)-β-conhydrine, (S)-(+)-pelletierine, and (S)-(-)-ropivacaine and the formal synthesis of ()-lasubine II and (+)-cermizine C.

PROCESS FOR THE PREPARATION OF (S)-ROPIVACAINE HYDROCHLORIDE MONOHYDRATE

Process for preparation of Ropivacaine hydrochloride monohydrate comprising resolution of racemic pipecoloxylidide in non-ketonic solvents to give (S)-pipecoloxylidide followed by N-propylation to in water ass reaction medium give (S)-Ropivacaine base; co

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.