27262-45-9

Basic information

• Product Name: (R)-(+)-BUPIVACAINE HCL
• Synonyms: D-(+)-Bupivacaine;d-Bupivacaine;(2R)-1-Butyl-N-(2,6-dimethylphenyl)piperidine-2β-carboxamide;(R)-(+)-BUPIVACAINE HCL;1-butyl-6’-pipecoloxylididd-(+)-2;(R)-(+)-Bupivacaine;2',6'-Pipecoloxylidide, 1-butyl-, (+)- (8CI);2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-, (2R)-
• CAS NO: 27262-45-9
• Molecular Formula: C₁₈H₂₈N₂O
• Molecular Weight: 288.43
• Product Categories: Chiral Standards
• Mol File: 27262-45-9.mol

Chemical Properties

• Boiling Point: 430.65°C (rough estimate)
• Flash Point: 209.9ºC
• Appearance: /
• Density: 1.0238 (rough estimate)
• Vapor Pressure: 2.24E-07mmHg at 25°C
• Refractive Index: 1.5700 (estimate)
• CAS DataBase Reference: (R)-(+)-BUPIVACAINE HCL(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-(+)-BUPIVACAINE HCL(27262-45-9)
• EPA Substance Registry System: (R)-(+)-BUPIVACAINE HCL(27262-45-9)

Safety Data

• Hazardous Substances Data: 27262-45-9(Hazardous Substances Data)

Usage

Uses

Used in Medical Applications:
(R)-(+)-BUPIVACAINE HCL is used as a local anesthetic for providing pain relief during surgical procedures and other medical interventions. It is particularly effective for epidural and intrathecal anesthesia, where it can be administered near the spinal cord to numb a specific region of the body, reducing the need for general anesthesia and its associated risks.
Used in Pain Management:
(R)-(+)-BUPIVACAINE HCL is also used for managing postoperative pain and other types of chronic pain. Its long-lasting anesthetic effect makes it a valuable option for patients who require extended periods of pain relief without the need for continuous administration.
Used in Obstetrics:
In the field of obstetrics, (R)-(+)-BUPIVACAINE HCL is used for providing pain relief during labor and delivery. It can be administered via an epidural injection, which helps to reduce the pain associated with contractions and childbirth, allowing for a more comfortable and controlled experience for the mother.
Used in Regional Anesthesia:
(R)-(+)-BUPIVACAINE HCL is employed in regional anesthesia for various surgeries, including orthopedic, vascular, and urological procedures. Its ability to block nerve conduction in a specific area makes it an ideal choice for surgeries that require localized pain relief without affecting the patient's consciousness or overall bodily function.

InChI:InChI=1/C18H28N2O/c1-4-5-12-20-13-7-6-11-16(20)18(21)19-17-14(2)9-8-10-15(17)3/h8-10,16H,4-7,11-13H2,1-3H3,(H,19,21)/t16-/m1/s1

Upstream product

• 4043-87-2 pipecolic Acid 
• 14252-80-3 racemic bupivacaine 
• 14252-80-3 bupivacaine hydrochloride 
• 109-65-9 1-bromo-butane 
• 27262-40-4 (S)-2',6'-pipecoloxylidide 
• 87-62-7 2,6-dimethylaniline 
• 98-98-6 2-Picolinic acid 
• 39627-98-0 2-pyridine-carboxamide-N-(2,6-dimethylphenyl) 
• 123-72-8 butyraldehyde 
• 856838-98-7 racemic 1-butylpiperidine-2-carboxylic acid 

Downstream Products

• 27262-47-1 levobupivacaine 
• 14252-80-3 racemic bupivacaine 

Relevant articles and documents

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.

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.

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.

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.

Enantioselective total syntheses of ropivacaine and its analogues

An alternative asymmetric synthesis of ropivacaine and analogues employing the 'cation pool' strategy and host/guest supramolecular co-catalysis approach is presented. In this study, chiral auxiliaries, several soft nucleophiles as well as one-pot conditions for anodic oxidation, followed by nucleophilic addition, have been applied.

Sustained-release liposomal anesthetic compositions

The invention provides a method for obtaining local anesthetics encapsulated in liposomes, such as multivesicular liposomes, with high encapsulation efficiency and slow release in vivo. When the encapsulated anesthetic is administered as a single intracutaneous dose, the duration of anesthesia and half-life of the drug at the local injection site is increased as compared to injection of unencapsulated anesthetic. The maximum tolerated dose of the encapsulated anesthetic is also markedly increased in the liposomal formulation over injection of unencapsulated anesthetic. These results show that the liposomal formulation of local anesthetic is useful for sustained local infiltration and nerve block anesthesia.

Bioreversible quaternary N-acyloxymethyl derivatives of the tertiary amines bupivacaine and lidocaine - Synthesis, aqueous solubility and stability in buffer, human plasma and simulated intestinal fluid

Design of water-soluble prodrugs may constitute a means to improve the oral bioavailability of drugs suffering from dissolution rate-limited absorption. The model drug bupivacaine containing a tertiary amine function has been converted into bioreversible quaternary N-acyloxymethyl derivatives. The pH-independent solubility of the N-butanoyloxymethyl derivate exceeded 1000 mg ml-1 corresponding approximately to a 10,000-fold increase in water solubility compared to that of bupivacaine base. The kinetics of hydrolysis of the prodrugs was studied in the pH range 0.1-9.8 (37°C). Decomposition was found to follow first-order kinetics and U-shaped pH-rate profiles were constructed. The observed differences between the hydrolytic lability of the derivatives might most likely be ascribed to steric effects. In most cases, the prodrugs were quantitatively converted into bupivacaine. However, for the hydrolysis of the N-butanoyloxymethyl derivative at neutral to slightly alkaline pH parallel formation of bupivacaine (～80%) and an unknown compound X (～20%) was observed. LC-MS analysis of the latter compound suggests that an aromatic imide structure has been formed from an intramolecular acyl transfer reaction involving a nucleophilic attack of the amide nitrogen atom on the ester carbonyl carbon atom. Whereas the derivatives were poor substrates for plasma enzymes; they were hydrolyzed rapidly to parent bupivacaine in the presence of pancreatic enzymes (simulated intestinal fluid) at 37°C. The data indicate that such prodrugs possess sufficient stability in the acidic environment of the stomach to reach the small intestine in intact form where they can be cleaved efficiently by action of pancreatic enzymes prior to drug absorption. Thus, the N-acyloxymethyl approach might be of potential utility to enhance oral bioavailability of tertiary amines exhibiting pKa values below approximately 6 and intrinsic solubilities in the low μM range.

PHARMACOLOGICALLY ACTIVE SALTS

Novel salts formed between two active drug substances, wherein the first drug substance is an NSAID drug substance containing a carboxylic acid group and the second drug substance contains an amine group and is a local anaesthetic or selected from the group consisting of non-opioid analgesics, antipsychotics, antidepressants, narcotic antagonists and local anaesthetics. Such salts that are poorly soluble in tissue fluids are feasible for injectable prolonged release formulations where the NSAID additionally to minimize pain and tissue reaction at the site of administration.