67686-01-5

Basic information

• Product Name: (1-Benzyl-4-piperidyl)methanol
• Synonyms: (1-BENZYLPIPERIDIN-4-YL)METHANOL;1-BENZYL-4-PIPERIDINEMETHANOL;(1-BENZYL-4-PIPERIDINYL)METHANOL;(1-BENZYL-4-PIPERIDYL)METHANOL;1-BENZYL-4-(HYDROXYMETHYL)PIPERIDINE;BUTTPARK 27\04-75;1-Benzyl-4-Piperdinemethanol;1-Benzy-4-HydroxymethylPiperidine
• CAS NO: 67686-01-5
• Molecular Formula: C₁₃H₁₉NO
• Molecular Weight: 205.3
• Product Categories: pharmacetical;Alcohol Aldehyde & acid series;Piperidine;Heterocyclic Compounds;Non-Chiral heterocyclic compounds
• Mol File: 67686-01-5.mol

Chemical Properties

• Boiling Point: 135-138°C (0.2 mmHg)
• Flash Point: 139.8 °C
• Appearance: /
• Density: 1.056 g/cm³
• Vapor Pressure: 0.00023mmHg at 25°C
• Refractive Index: 1.551
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 14.94±0.10(Predicted)
• CAS DataBase Reference: (1-Benzyl-4-piperidyl)methanol(CAS DataBase Reference)
• NIST Chemistry Reference: (1-Benzyl-4-piperidyl)methanol(67686-01-5)
• EPA Substance Registry System: (1-Benzyl-4-piperidyl)methanol(67686-01-5)

Safety Data

• Hazard Codes: Xi,T
• Statements: 25
• Safety Statements: 24/25-45
• HazardClass: IRRITANT
• Hazardous Substances Data: 67686-01-5(Hazardous Substances Data)

Usage

Synthesis

Charge toluene (100 mL) in a round bottom flask along with vitride (26 g, 0.12 mol) in an inert atmosphere. N-Benzyl ethyl isonipecotate (40 g, 0.16 mol) was added slowly in portions to the reaction mass. The mixture was stirred at room temperature for 2 h. After completion of the reaction the mass was quenched with chilled water. Toluene phase was separated and dried over anhydrous sodium sulfate. Toluene was removed under vacuum to get (1-Benzyl-4-piperidyl)methanol( 26.9 g, 82 %).

Chemical Properties

Colorless liquid

InChI:InChI=1/C13H19NO/c15-11-13-6-8-14(9-7-13)10-12-4-2-1-3-5-12/h1-5,13,15H,6-11H2

Upstream product

• 100-44-7 benzyl chloride 
• 10315-07-8 N-benzylpiperidine-4-carboxylic acid 
• 32018-56-7 1-benzyl-4-methyl-1 ,2,3,6-tetrahydropyridine 
• 22065-85-6 N-benzyl-4-formylpiperidine 
• 100-39-0 benzyl bromide 
• 498-94-2 isonipecotic acid 
• 3612-20-2 1-phenylmethyl-4-piperidone 
• 616897-44-0 2-(1-benzylpiperidin-4-ylidene)malononitrile 
• 1484-13-5 9-vinyl-9H-carbazole 
• 6457-49-4 4-piperidinemethanol 
• 100-52-7 benzaldehyde 
• 100-51-6 benzyl alcohol 
• 895578-02-6 1-benzyl-3-fluoro-4-hydroxymethyl-1,2,5,6-tetrahydropyridine 
• 895578-01-5 1-benzyl-3-fluoro-4-hydroxymethyl-1,2,5,6-tetrahydropyridine hydrochloride 

Downstream Products

• 67686-03-7 1-benzyl-4-chloromethylpiperidine hydrochloride 
• 120014-33-7 1-Benzyl-4-(methoxymethylidene)-piperidine 
• 120014-07-5 1-benzyl-4-<(5,6-dimethoxy-1-oxoindan-2-ylidenyl)methyl>piperidine 
• 142057-77-0 donepezil hydrochloride 
• 40240-12-8 1-benzyl-1,2,3,6-tetrahydropyridine 

Relevant articles and documents

In situ silane activation enables catalytic reduction of carboxylic acids

We describe a catalytic system for the conversion of carboxylic acids into alcohols using substoichiometric zinc acetate and N-methyl morpholine, in combination with phenylsilane as the nominal terminal reductant. Reaction monitoring by19F NMR spectroscopy demonstrates that the reaction proceeds by mutual activation of the carboxylic acid and silane through the in situ generation of silyl ester intermediates.

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).

Cobalt-Catalyzed Remote Hydroboration of Alkenyl Amines

We here present a generally applicable cobalt-catalyzed remote hydroboration of alkenyl amines, providing a practical strategy for the preparation of borylamines and aminoalcohols. This method shows broad substrate scope and good functional group tolerance, tolerating a series of alkenyl amines, including alkyl-alkyl amines, alkyl-aryl amines, aryl-aryl amines, and amides. Of note, this protocol is also compatible with a variety of natural products and drug derivatives. Preliminary mechanistic studies suggest that this transformation involves an iterative chain walking and hydroboration sequence.

Synthesis and Bio-Evaluation of N-Benzylpiperidine-8-Hydroxyquinoline Derivatives as Potential Cholinesterase Inhibitors, Metal Ion Chelators and Calcium Channel Blockers

Abstract: A new series of N-benzylpiperidine 8-hydroxyquinoline derivatives were synthesized and evaluated as cholinesterase inhibitors, metal ion chelators and calcium channel blockers. It was found that the ethyl cholinesterase inhibition activity could be improved when the linker between N-benzylpiperidine and 8?hydroxyquinoline groups were extended. Among all derivatives, compound (XIIId) showed best acetyl cholinesterase inhibition activity with an IC50 value of 0.24 ± 0.03 μM. It also showed metal ion chelating activity with a metal-compound ratio of 1 : 2 on copper or zinc ions. The calcium channel blocking property of select compounds were tested and compared by patching clamp on HEK293 cell expressing Cav1.2 calcium channel. Among tested compounds, cholinesterase inhibitor 8c showed mild calcium channel blockade activity with the inhibition ratio of calcium channel of 24.56 ± 2.44% (10 μM). This result suggested that the potential neuroprotective ability of this cholinesterase inhibitor might be partially related to the calcium channel blocking property.

Synthesis method of N-benzyl-4-piperidine formaldehyde

The invention belongs to the technical field of medicine synthesis, and particularly relates to a synthesis method of N-benzyl-4-piperidine formaldehyde. According to the invention, 4-piperidinecarboxylic acid is used as a raw material; an esterification reaction is carried out to generate 4-methyl piperidinecarboxylate hydrochloride; an alkylation reaction is carried out on N-benzyl-4-methyl piperidinecarboxylate hydrochloride to generate N-benzyl-4-methyl piperidinecarboxylate; n-benzyl-4-methyl piperidinecarboxylate is hydrolyzed to obtain N-benzyl-4-piperidinecarboxylic acid, N-benzyl-4-piperidinecarboxylic acid is subjected to an acylation reaction to generate N-benzyl-4-piperidinecarboxamide, N-benzyl-4-piperidinecarboxamide is dehydrated to obtain 1-benzylpiperidine-4-nitrile, and 1-benzylpiperidine-4-nitrile is subjected to a reduction reaction to generate N-benzyl-4-piperidineformaldehyde. The method is mild in reaction condition, simple in aftertreatment and high in yield, N-benzyl-4-piperidinecarboxaldehyde can be obtained at the high yield at the temperature of 0 DEG C, column chromatography is not needed, and repeatability is high.

Functional Group Interconversion of Alkylidenemalononitriles to Primary Alcohols by a Cooperative Redox Operation

Functional group interconversions are essential chemical processes enabling synthesis. In this report, we describe a strategy to convert alkylidenemalononitriles into primary alcohols in one step. The reaction relies on a choreographed redox process invol

N-alkylpiperidine carbamates as potential anti-Alzheimer's agents

Compounds capable of interacting with single or multiple targets involved in Alzheimer's disease (AD) pathogenesis are potential anti-Alzheimer's agents. In our aim to develop new anti-Alzheimer's agents, a series of 36 new N-alkylpiperidine carbamates was designed, synthesized and evaluated for the inhibition of cholinesterases [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)] and monoamine oxidases [monoamine oxidase A (MAO-A and monoamine oxidase B (MAO-B)]. Four compounds are very promising: multiple AChE (IC50 = 7.31 μM), BChE (IC50 = 0.56 μM) and MAO-B (IC50 = 26.1 μM) inhibitor 10, dual AChE (IC50 = 2.25 μM) and BChE (IC50 = 0.81 μM) inhibitor 22, selective BChE (IC50 = 0.06 μM) inhibitor 13, and selective MAO-B (IC50 = 0.18 μM) inhibitor 16. Results of enzyme kinetics experiments showed that despite the carbamate group in the structure, compounds 10, 13, and 22 are reversible and non-time-dependent inhibitors of AChE and/or BChE. The resolved crystal structure of the complex of BChE with compound 13 confirmed the non-covalent mechanism of inhibition. Additionally, N-propargylpiperidine 16 is an irreversible and time-dependent inhibitor of MAO-B, while N-benzylpiperidine 10 is reversible. Additionally, compounds 10, 13, 16, and 22 should be able to cross the blood-brain barrier and are not cytotoxic to human neuronal-like SH-SY5Y and liver HepG2 cells. Finally, compounds 10 and 16 also prevent amyloid β1–42 (Aβ1–42)-induced neuronal cell death. The neuroprotective effects of compound 16 could be the result of its Aβ1–42 anti-aggregation effects.

Industrially scalable synthesis of anti-alzheimer drug donepezil

This paper describes a simple, efficient and industrially scalable total synthesis of donepezil hydrochloride. The article also reported the X-ray studies of the 2-(1-benzylpiperidin-4-ylmethyliden)-5,6-dimethoxyindan-1-one, an intermediate in the synthesis of donepezil. The crystal structure analysis of 2-(1-benzylpiperidin-4-ylmethyliden)-5,6-dimethoxyindan-1-one shows that it crystallizes in monoclinic class under the space group P121/c1 with cell parameters, a = 17.2992(7) ?, b = 10.1999(4) ?, c = 11.9539(5) ?, β = 103.450(2)°, V = 2051.42(15) ?3 and Z = 4.

Compounding method for N-ethyl carbazole

The invention provides a compounding method for N-ethyl carbazole and relates to N-ethyl carbazole. The method comprises the following steps: performing salt-forming reaction on carbazole and proton-removing agent in an N-methyl pyrrolidone solvent, thereby generating carbazole salt; continuing introducing acetylene and reacting, thereby acquiring N-vinyl carbazole; adding a Pd catalyst into the organic solvent of the generated N-vinyl carbazole and performing hydrogenation reaction in the additives, thereby acquiring N-ethyl carbazole. A series of special catalysts are optimized, a catalytic hydrogenation technology is adopted for effectively realizing the green synthesis of N-ethyl carbazole and three-waste emission is reduced. In a hydrogenation process, the catalyst is reusable and the cost is lowered. The quality of the N-ethyl carbazole product prepared according to the hydrogenation process is higher. The traditional alkylate reagent (diethyl sulfate, ethyl carbonate, halothane, and the like) or the toxic organic solvent is not required, no waste liquid is emitted and the compounding method is a green and clean production technology.

Novel method for preparing donepezil

The present invention relates to a method for preparing Donepezil, comprising the steps of: (a) making 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-indene-2-carbonitrile represented by chemical formula 3 react with a benzylpiperidine compound represented by chemical formula 4 to provide 2-((1-benzylpiperidine-4-yl)methyl)-5,6-dimethoxy-1-oxo-2,3-dihydro-1H-indene-2-carbonitrile represented by chemical formula 2; and (b) subjecting 2-((1-benzylpiperidine-4-yl)methyl)-5,6-dimethoxy-1-oxo-2,3-dihydro-1H-indene-2-carbonitrile represented by chemical formula 2 to decyanation reaction, thereby providing Donepezil represented by chemical formula 1.COPYRIGHT KIPO 2017