24228-40-8

Basic information

• Product Name: Ethyl 1-benzylpiperidine-4-carboxylate
• Synonyms: RARECHEM AH CK 0037;AKOS 225-01;1-BENZYLPIPERIDINE-4-CARBOXYLIC ACID ETHYL ESTER;ETHYL 1-BENZYL-4-PIPERIDINECARBOXYLATE;ETHYL 1-BENZYLPIPERIDINE-4-CARBOXYLATE;BUTTPARK 33\04-91;Benzylpiperidinecarboxylicacidethylester;N-Benzyl-4-cabethoxypiperidine
• CAS NO: 24228-40-8
• Molecular Formula: C₁₅H₂₁NO₂
• Molecular Weight: 247.33
• EINECS: 246-094-9
• Product Categories: Piperidine;Heterocyclic Compounds;Aromatics;Heterocycles
• Mol File: 24228-40-8.mol
• Article Data: 46

Chemical Properties

• Melting Point: 120-119℃
• Boiling Point: 122°C (0.5 mmHg)
• Flash Point: >110℃
• Appearance: colourless oil
• Density: 1.037 g/mL at 25 °C
• Vapor Pressure: 0.000208mmHg at 25°C
• Refractive Index: 1.5120-1.5160
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: 7.93±0.10(Predicted)
• CAS DataBase Reference: Ethyl 1-benzylpiperidine-4-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl 1-benzylpiperidine-4-carboxylate(24228-40-8)
• EPA Substance Registry System: Ethyl 1-benzylpiperidine-4-carboxylate(24228-40-8)

Safety Data

• Hazard Codes: Xi,T
• Statements: 36/37/38-25
• Safety Statements: 24/25-45
• RIDADR: UN 2810 6.1 / PGIII
• Hazardous Substances Data: 24228-40-8(Hazardous Substances Data)

Usage

Synthesis

Ethyl isonipecotate (50 g, 0.31 mol) was dissolved in toluene (150 mL) in a round bottom flask, charged with potassium carbonate (60 g, 0.43 mol) and stirred for 15 min. Benzyl chloride (42 g, 0.31 mol) was charged and the reaction mass was refluxed for 4 h at 100 °C. Upon completion of the reaction as marked by TLC (hexane:ethyl acetate; 2:1), the reaction mass was cooled to room temperature and quenched with water (100 mL), stirred and the organic phase was separated. The aqueous phase was again extracted with toluene (100 mL). Combined organic phase was washed twice with saturated brine solution (50 mL). Remove toluene in vacuo to obtain Ethyl N-benzylpiperidine-4-carboxylate ( 6.97 g, 91 %) as a yellow liquid.

Chemical Properties

Colourless Oil

InChI:InChI=1/C15H21NO2/c1-2-18-15(17)14-8-10-16(11-9-14)12-13-6-4-3-5-7-13/h3-7,14H,2,8-12H2,1H3

Upstream product

• 1126-09-6 4-carbethoxypiperidine 
• 100-39-0 benzyl bromide 
• 100-44-7 benzyl chloride 
• 100-51-6 benzyl alcohol 
• 136081-74-8 ethyl 1-benzoyl-4-piperidine-carboxylate 
• 100-52-7 benzaldehyde 
• 23019-61-6 1-benzyl-4-(ethoxycarbonyl)pyridin-1-ium bromide 

Downstream Products

• 40117-97-3 8-benzyl-8-aza-2-oxaspiro<4.5>decan-1-one 
• 114399-88-1 α,α-diphenyl-1-(phenylmethyl)-4-piperidinemethanol 
• 117022-62-5 α,α-bis(4-methoxyphenyl)-1-(phenylmethyl)-4-piperidinemethanol 
• 117022-61-4 α,α-Bis(4-methylphenyl)-1-(phenylmethyl)-4-piperidinemethanol 
• 136709-51-8 ethyl 1-benzyl-4-hydrazino>piperidine-4-carboxylate 
• 67686-01-5 1-benzyl-4-piperidinemethanol 
• 74045-91-3 1-benzyl-piperidine-4-carboxylic acid hydrazide 
• 111627-25-9 α,α-bis-(4-fluorophenyl)-1-(phenylmethyl)-4-piperidinemethanol 
• 22065-85-6 N-benzyl-4-formylpiperidine 
• 10315-07-8 N-benzylpiperidine-4-carboxylic acid 
• 117022-54-5 4-[α,α-Bis(3-fluorophenyl)hydroxymethyl]-1-phenylmethylpiperidine fumarate 
• 299428-04-9 N-benzyl-4-(2-hydroxy-2-propyl)piperidine 
• 76876-70-5 N-benzyl-4-(2-hydroxyethyl)piperidine 

Relevant articles and documents

First synthesis of racemic trans propargylamino-donepezil, a pleiotrope agent able to both inhibit AChE and MAO-B, with potential interest against Alzheimer’s disease

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease towards which pleiotropic approach using Multi-Target Directed Ligands is nowadays recognized as probably convenient. Among the numerous targets which are today validated against AD, acetylcholinesterase (ACh) and Monoamine Oxidase-B (MAO-B) appear as particularly convincing, especially if displayed by a sole agent such as ladostigil, currently in clinical trial in AD. Considering these results, we wanted to take benefit of the structural analogy lying in donepezil (DPZ) and rasagiline, two indane derivatives marketed as AChE and MAO-B inhibitors, respectively, and to propose the synthesis and the preliminary in vitro biological characterization of a structural compromise between these two compounds, we called propargylaminodonepezil (PADPZ). The synthesis of racemic trans PADPZ was achieved and its biological evaluation established its inhibitory activities towards both (h)AChE (IC50 = 0.4 μM) and (h)MAO-B (IC50 = 6.4 μM).

Basic Anion-Exchange Resin-Catalyzed Aldol Condensation of Aromatic Ketones with Aldehydes in Continuous Flow

A general method for the aldol condensation of aromatic ketones with aldehydes was developed under continuous-flow conditions using a commercially available, strongly basic anion-exchange resin (A26) as catalyst. This procedure, in addition to exhibiting a wide substrate scope, promoted carbon-carbon bond formation under mild conditions using a quasi-stoichiometric ratio of starting reagents with good to excellent yields, thereby forming a limited amount of waste and allowing the process to be applied to sequential-flow systems. A proof of concept was developed in the first fully heterogeneously catalyzed two-step flow synthesis of donepezil, which is a blockbuster commercial anti-Alzheimer's drug.

Novel N-benzylpiperidine carboxamide derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer's disease

A series of fifteen acetylcholinesterase inhibitors were designed and synthesised based upon the previously identified lead compound 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (5) which showed good inhibitory activity (IC50 0.03 ± 0.07 μM) against acetylcholinesterase. A series of compounds were prepared wherein the ester linker in the original lead compound was exchanged for a more metabolically stable amide linker and the indanone moiety was exchanged for a range of aryl and aromatic heterocycles. The two most active analogues 1-benzyl-N-(5,6-dimethoxy-8H-indeno[1,2-d]thiazol-2-yl)piperidine-4-carboxamide (28) and 1-benzyl-N-(1-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) piperidine-4-carboxamide (20) afforded in vitro IC50 values of 0.41 ± 1.25 and 5.94 ± 1.08 μM, respectively. In silico screening predicts that 20 will be a blood brain-barrier permeant, and molecular dynamic simulations are indicative of a close correlation between the binding of 20 and the Food and Drug Administration-approved cholinesterase inhibitor donepezil (1).