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
• Article Data: 22

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

Chemical Properties

White Solid

Originator

Chirocaine,Abbott Laboratories

Uses

Local anaesthetic used for epidural and intrathecal anaesthesia.

Therapeutic Function

Local anesthetic

General Description

Levobupivacaine is the pure “S” enantiomer of bupivacaineand in vivo and in vitro studies confirm that it does notundergo metabolic inversion to R(+) bupivacaine. The pKaof the tertiary nitrogen is 8.09, the same as bupivacaine’s pKa. Levobupivacaine is available in solution for epiduraladministration, peripheral nerve block administration, andinfiltration anesthesia. Clinical trials have shown thatlevobupivacaine and bupivacaine have similar anestheticeffects. Levobupivacaine has lower CNS and cardiotoxicitythan bupivacaine although unintended intravenousinjection when performing nerve blocks may result intoxicity. Racemic bupivacaine is metabolized extensivelywith no unchanged drug found in the urine or feces. Liverenzymes including the CYP3A4 and CYP1A2 isoforms areresponsible for N-dealkylation and 3-hydroxylation oflevobupivacaine followed by glucuronidation or sulfation.

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

• 27262-45-9 (+)-Bupivacaine 
• 542-69-8 1-iodo-butane 
• 27262-40-4 (S)-2',6'-pipecoloxylidide 
• 14252-80-3 bupivacaine hydrochloride 
• 856838-98-7 racemic 1-butylpiperidine-2-carboxylic acid 
• 87-62-7 2,6-dimethylaniline 
• 109-65-9 1-bromo-butane 
• 98-98-6 2-Picolinic acid 
• 39627-98-0 2-pyridine-carboxamide-N-(2,6-dimethylphenyl) 
• 123-72-8 butyraldehyde 
• 67-66-3 chloroform 
• 3105-95-1 pipecolinic acid 
• 856838-98-7 (2S)-1-butylpiperidine-2-carboxylic acid 
• 26250-84-0 (S)-(-)-1-(tert-butoxycarbonyl)-2-piperidinecarboxylic acid 

Downstream Products

• 27262-45-9 (+)-Bupivacaine 

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.

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.

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%.