27262-47-1

Basic information

• Product Name: 1-Butyl-N-(2,6-dimethylphenyl)-piperidine-2-carboxamide
• Synonyms: 1-Butyl-N-(2,6-dimethylphenyl)-piperidine-2-carboxamide;Chirocaine;Levobupivacaine;(2S)-1-Butyl-N-(2,6-dimethylphenyl)piperidine-2α-carboxamide;2',6'-Pipecoloxylidide, 1-butyl-, L-(-)-;1-Butyl-N-(2,6-dimet;Levobupivacaine base;(2S)-1-Butyl-N-(2,6-diMethylphenyl)-2-piperidinecarboxaMide
• CAS NO: 27262-47-1
• Molecular Formula: C₁₈H₂₈N₂O
• Molecular Weight: 288.43
• EINECS: 1533716-785-6
• Product Categories: Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Inhibitors
• Mol File: 27262-47-1.mol

Chemical Properties

• Melting Point: 136-137°C
• Boiling Point: 430.65°C (rough estimate)
• Flash Point: 209.9 °C
• Appearance: /
• Density: 1.0238 (rough estimate)
• Refractive Index: 1.5700 (estimate)
• Storage Temp.: Refrigerator
• PKA: 14.85±0.70(Predicted)
• CAS DataBase Reference: 1-Butyl-N-(2,6-dimethylphenyl)-piperidine-2-carboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Butyl-N-(2,6-dimethylphenyl)-piperidine-2-carboxamide(27262-47-1)
• EPA Substance Registry System: 1-Butyl-N-(2,6-dimethylphenyl)-piperidine-2-carboxamide(27262-47-1)

Safety Data

• Hazardous Substances Data: 27262-47-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1-Butyl-N-(2,6-dimethylphenyl)-piperidine-2-carboxamide is used as a local anesthetic for epidural and intrathecal anesthesia due to its ability to provide effective pain relief with lower risks of central nervous system (CNS) and cardiotoxicity compared to other anesthetic agents.
Used in Chemical Research:
As a white solid with unique chemical properties, 1-Butyl-N-(2,6-dimethylphenyl)-piperidine-2-carboxamide can be utilized in chemical research and development for the synthesis of new compounds or as an intermediate in the production of various pharmaceuticals and chemicals.
Used in Drug Metabolism Studies:
The compound's metabolic profile, including its pKa value and the enzymes responsible for its N-dealkylation and 3-hydroxylation, makes it a valuable subject for drug metabolism studies. Understanding its metabolic pathways can contribute to the development of safer and more effective drugs.

Originator

Chirocaine,Abbott Laboratories

Therapeutic Function

Local anesthetic

Pharmacology

This is the laevo (S–) enantiomer of bupivacaine, with similar properties to the racemic mixture, though it has slightly higher protein binding and clearance and hence a lower potential for cardiac and CNS toxicity. In practice, several other factors contribute to local anaesthetic toxicity, and the recommended maximum doses remain the same. Its formulation is expressed as percentage weight per unit volume of free base; racemic bupivacaine is expressed as percentage weight per unit volume of hydrochloride salt. Levobupivacaine therefore contains 13% more active molecules for a given dose.

InChI:InChI=1/C9H19N.C7H7NO.C2H6.ClH/c1-2-3-7-10-8-5-4-6-9-10;9-6-8-7-4-2-1-3-5-7;1-2;/h2-9H2,1H3;1-6H,(H,8,9);1-2H3;1H

Upstream product

• 109-65-9 1-bromo-butane 
• 14252-80-3 bupivacaine hydrochloride 
• 27262-45-9 (+)-Bupivacaine 
• 856838-98-7 racemic 1-butylpiperidine-2-carboxylic acid 
• 87-62-7 2,6-dimethylaniline 
• 4043-87-2 pipecolic Acid 
• 39627-98-0 2-pyridine-carboxamide-N-(2,6-dimethylphenyl) 
• 123-72-8 butyraldehyde 
• 98-98-6 2-Picolinic acid 
• 27262-40-4 (S)-2',6'-pipecoloxylidide 
• 14252-80-3 racemic bupivacaine 
• 16819-50-4 N-(2,6-dimethylphenyl)benzylamine 
• 125486-26-2 N-benzyl-2-chloro-N-(2,6-dimethyl-phenyl)-acetamide 
• 830326-44-8 2-azido-N-benzyl-N-(2,6-dimethyl-phenyl)-acetamide 

Downstream Products

• 27262-45-9 (+)-Bupivacaine 

Relevant articles and documents

Preparation method of bupivacaine and intermediate (S)-2-piperidinecarboxylic acid thereof

The invention discloses bupivacaine and a preparation method of an intermediate (S)-2-piperidinecarboxylic acid of the bupivacaine; wherein the intermediate (S)-2-piperidinecarboxylic acid is prepared by taking (R)-4-benzyl-2-oxazolidinone as a chiral auxiliary agent through amidation, asymmetric alkylation, hydrolysis, cyclization and auxiliary group removal; wherein the prepared (S)-2-piperidinecarboxylic acid is used as a raw material to prepare the local anesthetic (S)-bupivacaine. The method utilizes cheap and easily available organic raw materials, and has the advantages of simple operation, mild reaction conditions, good stereoselectivity, high yield and the like.

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.

Levobupivacaine intermediate compound

The invention belongs to the technical field of medicine synthesis, and particularly relates to a levobupivacaine intermediate compound. The preparation method comprises the following steps: reacting 2-chloropiperidine containing S configuration with n-butyl bromide to generate a novel intermediate compound IV containing S configuration. The novel levobupivacaine intermediate compound IV provided by the invention does not generate larger impurities in the subsequent substitution reaction for preparing levobupivacaine, the levobupivacaine obtained by utilizing the novel intermediate avoids condensation of traditional carboxyl and amido and avoids resolution, and the obtained product is also higher in purity.

Insoluble complex, pharmaceutical composition and application of pharmaceutical composition

The invention provides an insoluble complex shown in a formula (I), a pharmaceutical composition and application of the pharmaceutical composition in preventing or treating pain during and after operations. According to the technical scheme, a medicine which is simple in production process and capable of stably releasing local anesthesia medicines in bodies for a long term is provided, the medicine can release local anesthesia medicines for 3 days or longer, can prolong a pain relieving function after operations, can be used by doctors and patients conveniently, and has good medication compliance.

Enantioseparation of racemic bupivacaine via ultrasonic-assisted diastereomeric crystallization using 12,14-dinitrodehydroabietic acid

12,14-Dinitrodehydroabietic acid (12,14-dinitroDHAA), a chiral acid obtained by the nitration of optical dehydroabietic acid (DHAA), was successfully employed as resolving agent. The resolution of racemic bupivacaine by ultrasonic-assisted diastereomeric crystallization in ethanol was investigated. The results indicated that ultrasonic-assist can well facilitate resolution of (R,S)-bupivacaine and a higher enantiomeric excess (ee) and yield was obtained for (S)-bupivacaine, and while without ultrasound, the ee value decreases by increasing the crystallization time. A Box-Behnken experimental design with four factors (amount of 12,14-dinitroDHAA, ethanol amount, ultrasonic power and crystallization temperature) combined with response surface methodology (RSM) was applied to explore resolution effects. A second-order polynomial equation was adequate to model the relationship between the ee (or yield) and the dependent variables. When maintaining a lower limit of 90% for the yield of (S)-bupivacaine, the optimal resolution conditions by RSM were 12,14-dinitroDHAA/bupivacaine molar ratio of 1.6, solvent/propranolol ratio of 16.5 mL/g, 63.2 W ultrasonic power and crystallization temperature of 0 °C, respectively. Under the optimal conditions, the experimental ee and yield of (S)-bupivacaine were 69.8% and 87.5%.

HYDROPHOBIC ACID ADDITION SALTS AND PHARMACEUTICAL FORMULATIONS THEREOF

The invention provides hydrohphobic drug salts and pharmaceutical compositions comprising such salts. The invention fourther provides compositions for delivering poorly soluble drugs, including hydrophobic drug salts.

Preparation method of levobupivacaine hydrochloride

The invention belongs to the technical field of chemical synthesis and particularly relates to a preparation method of levobupivacaine hydrochloride. The preparation method comprises the steps of carrying out catalytic hydrogenation on racemic or S-form 2-piperidinecarboxylicacid as a raw material and n-butanal so as to obtain 1-butylpiperidine-2-carboxylic acid, carrying out condensation reaction on 1-butylpiperidine-2-carboxylic acid and 2,6-dimethylaniline so as to generate bupivacaine or levobupivacaine, and carrying out subsequent treatment, so as to obtain a final product, namely levobupivacaine hydrochloride. Compared with existing synthetic routes, the preparation method has the advantages that the synthetic route is short, the method is simple, convenient in operation, low in cost and easy for industrial production, reaction conditions of each step are relatively mild, the process is stable, a strong-corrosion chlorinated reagent is not used, and the environmental pollution is reduced.

Preparation method of levobupivacaine hydrochloride

The invention belongs to the technical field of chemical synthesis and in particular relates to a preparation method of levobupivacaine hydrochloride. The preparation method takes racemic or S-configuration 2-piperidinecarboxylic acid as a starting raw material and comprises the following steps: taking the starting raw material and n-butylaldehyde to react and carrying out borohydride reduction reaction to obtain 1-butylpiperidine-2-carboxylic acid; taking the 1-butylpiperidine-2-carboxylic acid and 2,6-dimethylaniline to be subjected to condensation reaction, so as to generate bupivacaine or levobupivacaine; carrying out subsequent treatment to obtain a final product levobupivacaine hydrochloride. Compared with an existing synthesis route, the preparation method has the advantages of short synthesis route, simple method, convenience for operation, low cost and easiness for industrial production; reaction conditions of each step are relatively moderate, a process is stable, a strong-corrosion chlorination reagent is not used, the pollution to environment is reduced and the like.

Synthesis of Mepivacaine and Its Analogues by a Continuous-Flow Tandem Hydrogenation/Reductive Amination Strategy

Herein we report a convenient, fast, and high-yielding method for the generation of the racemic amide anaesthetics mepivacaine, ropivacaine, and bupivacaine. Coupling of α-picolinic acid and 2,6-xylidine under sealed-vessel microwave conditions generates the intermediate amide after a reaction time of only 5 min at 150 °C. Subsequent reaction in a continuous-flow high-pressure hydrogenator (H-Cube ProTM) in the presence of the respective aldehyde directly converts the intermediate to the final amide anaesthetics in a continuous, integrated, multi-step ring-hydrogenation/reductive amination protocol. Merits and limitations of the protocol are discussed.

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.