15883-20-2

Basic information

• Product Name: 2',6'-Pipecoloxylidide
• Synonyms: Pipecolinoyl-2,6-xylidide;N-(2',6'-dimethylphenyl)-piperidine-2- carboxylic amide;Des-butyl Bupivacaine (Bupivacaine metabolite);Desbutylbupivacain;N-(2',6'-Dimethylphenyl)-2-Pip;(2RS)-N-(2,6-DIMETHYLPHENYL) -2-PIPERIDINE CARBOXAMIDE;2',6'-Pipecoloxylidide;N-(2,6-Dimethylphenyl)-2-piperidinecarboxamide
• CAS NO: 15883-20-2
• Molecular Formula: C₁₄H₂₀N₂O
• Molecular Weight: 232.32
• EINECS: 1308068-626-2
• Product Categories: Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 15883-20-2.mol

Chemical Properties

• Melting Point: 114-1170C
• Boiling Point: 392.3 ºC at 760 mmHg
• Flash Point: 149 ºC
• Appearance: Off-white to light yellow powder
• Density: 1.087 g/cm³
• Storage Temp.: -20°C Freezer
• PKA: 14.85±0.70(Predicted)
• CAS DataBase Reference: 2',6'-Pipecoloxylidide(CAS DataBase Reference)
• NIST Chemistry Reference: 2',6'-Pipecoloxylidide(15883-20-2)
• EPA Substance Registry System: 2',6'-Pipecoloxylidide(15883-20-2)

Safety Data

• Hazard Codes: Xi,T
• Statements: 25
• Safety Statements: 45
• RIDADR: UN 2811 6.1 / PGIII
• RTECS: TM6076000
• Hazardous Substances Data: 15883-20-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2',6'-Pipecoloxylidide is used as an impurity reference substance for Bupivacaine (B689561), a sodium channel blocker and local anesthetic. Its presence in the pharmaceutical industry is crucial for quality control and ensuring the safety and efficacy of Bupivacaine-based medications.
Used in Anesthetic Applications:
As a metabolite of Bupivacaine, 2',6'-Pipecoloxylidide plays a role in the anesthetic process, contributing to the overall effectiveness of the local anesthetic in medical and surgical procedures. Its understanding and study can help improve the development of new anesthetic agents and enhance patient care.
Used in Research and Development:
2',6'-Pipecoloxylidide serves as a valuable compound for researchers in the field of pharmaceuticals and medicinal chemistry. It can be used to study the metabolic pathways of Bupivacaine and potentially develop new drugs with improved properties or reduced side effects.

Upstream product

• 110-52-1 1,4-dibromo-butane 
• 102881-97-0 2-amino-N-(2,6-dimethyl-phenyl)-malonamic acid ethyl ester 
• 39627-98-0 2-pyridine-carboxamide-N-(2,6-dimethylphenyl) 
• 98-98-6 2-Picolinic acid 
• 15960-82-4 ethyl 3-((2,6-dimethylphenyl)amino)-3-oxopropanoate 
• 100616-40-8 N-(2,6-dimethyl-phenyl)-2-hydroxyimino-malonamic acid ethyl ester 
• 87-62-7 2,6-dimethylaniline 
• 27262-40-4 (S)-2',6'-pipecoloxylidide 
• 67-63-0 isopropyl alcohol 
• 1537190-05-8 C₁₄H₂₀N₂O*C₁₆H₁₅NO₃ 
• 636-80-6 2-picolinic acid hydrochloride 
• 28697-07-6 N-benzyloxycarbonyl D/L-pipecolinic acid 
• 4043-87-2 pipecolic Acid 
• 67-56-1 methanol 

Downstream Products

• 27262-39-1 (S)-dibenzoyl-2-pipecolinoxylidide-L-tartrate 
• 27262-40-4 (S)-2',6'-pipecoloxylidide 
• 1364698-38-3 (R,S)-N-(2,6-dimethylphenyl)piperidinium-2-carboxamide bis-(trifluoromethylsulfonyl)imide 
• 78289-28-8 pipecolic-2-acid-2',6'-xylidide 
• 14252-80-3 bupivacaine hydrochloride 
• 98626-61-0 1-propyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide 

Relevant articles and documents

Design of an integrated process of chromatography, crystallization and racemization for the resolution of 2′,6′-pipecoloxylidide (PPX)

An integrated process for the chiral separation of the industrially relevant substance 2′,6′-pipecoloxylidide (PPX), an intermediate in the manufacture of a number of anesthetics, was developed. By combining three different techniques, chromatography, crystallization, and racemization, high productivity was achieved. All unit operations were executed using a common solvent system, full recycling, and a minimum of solvent exchanges or removals. The target molecule was obtained with an enantiopurity of >99.5 wt %.

Synthesis, biological evaluation, and molecular docking of ropivacaine analogs as local anesthetic agents

Two series of ropivacaine analogs (4a–4q, 7a–7c) were synthesized, and their biological activities were evaluated as local anesthetic agents. Most of the compounds displayed detectable local anesthetic characteristics. Among them, compound 4l showed significant efficacy with sciatic nerve block, infiltration, corneal surface, and spinal anesthetic activities. It was as potent as the reference compound ropivacaine. Dissociation constants of these compounds were 5.9–7.9. In addition, molecular docking modeling on compound 4l and ropivacaine was performed to delineate structural requirements and potential mechanisms for the local anesthetic activity. This study provides valuable new information for our ongoing endeavor to design more potent local anesthetics.

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 bupivacaine hydrochloride

The invention discloses a preparation method of bupivacaine hydrochloride. The preparation method includes the steps of: 1) preparing N-(2,6-xylyl)-2-piperidineformamide; 2) preparing the bupivacaine hydrochloride. The reaction routes in the two steps are described in the specification. The method has high yield, high product quality and low operation cost, allows automation operation of equipment, has good stability, and can satisfy industrial demands.

Topalgia treatment methods and compositions for treating

The invention relates to the compounds of formula (I) or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula (I), and methods for the treatment of local pain may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of infiltration, nerve block, epidural, intrathecal anesthesia, pain, severe pain, chronic pain, chemotherapy induced pain, neuropathic pain, post herpetic neuralgia, neuralgia, motor neurone disease, diabetic neuropathy, postheipetic neuralgia, injury, post-operative pain, osteoarthritis, rheumatoid arthritis, multiple sclerosis, spinal cord injury, migraine, HIV related neuropathic pain, cancer pain and Sower back pain.

Synthesis method of bupivacaine

The invention belongs to a synthesis method of bupivacaine. The method comprises: adding 2 piperidinecarboxylicacid into aqueous alkali, dropwise adding Cbz and alkaline water, after finishing dropwise adding at normal temperature, reacting for 12 hours, after reaction, extracting with diethyl ether, washing a water layer to be weak-acid with 18% of diluted hydrochloric acid, extracting with the diethyl ether again, combining an diethyl ether layer, drying and filtering, and concentrating to obtain a dried product; adding the dried product into a DMF solvent, then adding a catalyst for reaction for 1 hour at normal temperature, then adding 2,6-dimethylaniline, reacting for 18hours at normal temperature, adding water and ethyl acetate for washing, taking an organic layer, drying and filtering, and concentrating to obtain a dried concentrated product; adding the dried concentrated product into a solvent, then adding a catalyst, pressurizing and introducing hydrogen, filtering after reaction and concentrating to obtain a dried product; adding the product in the above step into a solvent, dropwise adding bromo-n-butane at normal temperature, after dropwise adding, rising temperature to 80 DEG C for reacting for 12 hours, adding diluted hydrochloric acid, slowing cooling to normal temperature, and crystallizing, filtering and drying to obtain the product. The synthesis method has the advantages of higher yield, smaller pollution and low equipment requirement.

A process for the preparation of ropivacaine hydrochloride

The invention provides a method for preparing hydrochloric acid ropivacaine. Part of parameters and conditions in the prior art are improved, and optimization is performed through the following steps that intermediate (I) separation pH and separation extracting solvent are selected; a catalyst and the usage quantity of the catalyst in a resolution agent are selected; refining solvent is selected. In this way, the yield and purity of the prepared hydrochloric acid ropivacaine are high, the purity reaches up to over 99% under the optimal condition, the percentage of dextrorotary isomer is reduced below 0.5%, standard requirements are completely met, and the hydrochloric acid ropivacaine is suitable for industrial production.

Compositions and methods for the treatment of local pain

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of local pain may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of infiltration, nerve block, epidural, intrathecal anesthesia, pain, severe pain, chronic pain, chemotherapy induced pain, neuropathic pain, post herpetic neuralgia, neuralgia, motor neurone disease, diabetic neuropathy, postherpetic neuralgia, injury, post-operative pain, osteoarthritis, rheumatoid arthritis, multiple sclerosis, spinal cord injury, migraine, HIV related neuropathic pain, cancer pain and lower back pain.

PROCESS FOR ENANTIOMERIC ENRICHMENT OF 2 ', 6 ' - PIPECOLOXYLIDIDE

The invention discloses a process for enantiomeric enrichment of 2',6'-pipecoloxylidide using a chiral carbamoyl benzoic acid to provide (S)-enantiomer in high yield and high enantiomeric purity. The invention also discloses novel intermediates formed in the process of enantiomeric enrichment of 2',6'-pipecoloxylidide, preparation of N- substituted amidic acids and alkylation of 2',6'-pipecoloxylidide.

PROCESS FOR PRODUCING PIPECOLIC-2-ACID-2 ',6'-XYLIDIDE USEFUL AS AN INTERMEDIATE FOR THE PREPARATION OF LOCAL ANESTHETICS

The present invention relates to an improved process for the preparation of pipecolic-2- acid-2',6'-xylidide or derivative thereof wherein it comprises hydrogenation of picolinic-2-acid-2',6'-xylidide in the presence of a Raney-nickel as a catalyst.