4727-72-4

Basic information

• Product Name: 1-Benzyl-4-hydroxypiperidine
• Synonyms: 4-HYDROXY-1-BENZYLPIPERIDINE;benzyl-4-piperidinol;4-Piperidinol, 1-(phenylmethyl)-;1-Benzyl-4-hydroxypiperidine,97%;NSC 72991;1-(Phenylmethyl)-4-piperidinol;1-Benzyl-piperidin-4-ol;4-Piperidinol, 1-benzyl-
• CAS NO: 4727-72-4
• Molecular Formula: C₁₂H₁₇NO
• Molecular Weight: 191.27
• EINECS: 225-226-9
• Product Categories: Alcohols and Derivatives;Non-Chiral heterocyclic compounds;Agro-Products;Aromatics;Heterocycles;Building Blocks;C12;Chemical Synthesis;Heterocyclic Building Blocks;Piperidines
• Mol File: 4727-72-4.mol

Chemical Properties

• Melting Point: 61-63 °C(lit.)
• Boiling Point: 127-128 °C2 mm Hg(lit.)
• Flash Point: 121-123°C/0.7mm
• Appearance: White to yellow/Crystalline Powder
• Density: 1.0096 (rough estimate)
• Vapor Pressure: 0.000738mmHg at 25°C
• Refractive Index: 1.5212 (estimate)
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Chloroform, Methanol
• PKA: 14.87±0.20(Predicted)
• Sensitive: Hygroscopic
• BRN: 146118
• CAS DataBase Reference: 1-Benzyl-4-hydroxypiperidine(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Benzyl-4-hydroxypiperidine(4727-72-4)
• EPA Substance Registry System: 1-Benzyl-4-hydroxypiperidine(4727-72-4)

Safety Data

• Hazard Codes: T,C,Xi,Xn
• Statements: 25-36/37/38-20/21/22
• Safety Statements: 26-45-37/39-36
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 2
• Hazardous Substances Data: 4727-72-4(Hazardous Substances Data)

Usage

Uses

1-Benzyl-4-hydroxypiperidine is used as a chemical intermediate for the synthesis of various pharmaceutical compounds, including:
Muscarinic acetylcholine receptor antagonists and beta 2 adrenoceptor agonists, which are used in the treatment of respiratory diseases and other conditions.
Fatty acid amide hydrolase inhibitors, which have potential therapeutic applications in pain management and neurodegenerative disorders.
PI3 kinase-alpha inhibitors, which are being investigated for their potential role in cancer treatment.
Flavonoid derivatives used as dual binding acetylcholinesterase inhibitors, which may have applications in the treatment of Alzheimer's disease and other cognitive disorders.
Urotensin-II receptor antagonists, which could be useful in the treatment of cardiovascular diseases.
Rho kinase inhibitors, which have potential applications in the treatment of various conditions, including glaucoma and hypertension.
Additionally, 1-Benzyl-4-hydroxypiperidine is used as a reactant in the synthesis of a piperidine-based pesticide, which is employed in the agricultural industry to protect crops from pests.
In the field of research, 1-Benzyl-4-hydroxypiperidine is used as an alternative molecule to study the ligand concentration attached to the epoxy-activated Sepharose 6B, which is a type of affinity chromatography resin used for protein purification and immobilization.
Overall, 1-Benzyl-4-hydroxypiperidine is a valuable chemical intermediate with diverse applications in the pharmaceutical, agricultural, and research industries, making it an important compound for the development of new drugs and chemical products.

Synthesis Reference(s)

Journal of the American Chemical Society, 108, p. 3512, 1986 DOI: 10.1021/ja00272a059

InChI:InChI=1/C12H17NO/c14-12-6-8-13(9-7-12)10-11-4-2-1-3-5-11/h1-5,12,14H,6-10H2/p+1

Upstream product

• 20821-52-7 1-benzyl-4-piperidone hydrochloride 
• 50-00-0 formaldehyd 
• 90284-71-2 N-benzylammonium trifluoroacetate 
• 762-72-1 allyl-trimethyl-silane 
• 100-46-9 benzylamine 
• 3046-49-9 [14C]formaldehyde 
• 17150-62-8 N-benzyl-3-butenylamine 
• 111865-51-1 N-[1-(4-methoxyphenyl)-3-butenyl]benzylamine 
• 111865-50-0 benzyl[1-(4-methylphenyl)but-3-enyl]amine 
• 99948-39-7 ethyl 2-(benzylamino)pent-4-enoate 
• 173416-02-9 (E)-N-benzyl-1-phenylhexa-1,5-dien-3-amine 
• 109-87-5 Dimethoxymethane 
• 88381-98-0 N-(1-phenyl-3-butenyl)benzylamine 
• 111865-49-7 N-benzyl-1-(4-chlorophenyl)-3-butenylamine 

Downstream Products

• 895148-76-2 3-(1-benzylpiperidin-4-yl)-5,5-dibenzyl-imidazolidine-2,4-dione 
• 936330-40-4 3-(1-benzylpiperidin-4-yl)-5,5-dicyclohexyl-imidazolidine-2,4-dione 
• 895148-80-8 3-(1-benzylpiperidin-4-yl)-5,5-di(2-thienyl)-imidazolidine-2,4-dione 
• 895148-74-0 3-(1-benzylpiperidin-4-yl)-5-phenyl-5-cyclohexyl-imidazolidine-2,4-dione 
• 895148-77-3 3-(1-benzylpiperidin-4-yl)-5,5-di-(4-methoxyphenyl)-imidazolidine-2,4-dione 
• 895148-72-8 3-(1-benzyl-piperidin-4-yl)-5,5-diphenyl-imidazolidine-2,4-dione 
• 101768-14-3 1-benzyl-4-piperidinyl 4-methylbenzenesulfonate 
• 895148-79-5 3-(1-benzylpiperidin-4-yl)-5,5-di-(4-fluorophenyl)-imidazolidine-2,4-dione 
• 791119-72-7 1-benzyl-4-(2,2'-dichlorobenzhydryloxy)piperidine 
• 720674-03-3 C₂₆H₁₈Cl₄O 
• 791119-48-7 1-benzyl-4-(2,4'-dichlorobenzhydryloxy)piperidine 
• 745066-51-7 1-(phenylmethyl)piperidin-4-yl butylcarbamate 
• 863249-61-0 2,2-dimethyl-propionic acid 1-benzyl-piperidin-4-yl ester 
• 171722-92-2 4-piperidyl N-(2-biphenyl)carbamate 

Relevant articles and documents

COMPOUNDS AND METHODS OF USE

Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X1, X2, X3, X4, X5, A, L, R1, R2, R5, m and n are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

Compounds and methods of use

Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X1, X2, X3, X4, Y, A, L1, L2, R1, R2, R5, m and n are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

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, identification and molecular docking studies of N-functionalized piperidine derivatives linked to 1,2,3-triazole ring

New derivatives of piperidine bearing a 1,2,3-triazole ring designed and synthesized smoothly over six steps from N-protected piperidone-4-one. These steps included reduction of the carbonyl group/tosylation of the resulting alcohol providing tosyl derivative in a good yield, followed by nucleophilic substitution and Cu-catalysed azide-alkyne cycloaddition. By removing the protecting group and functionalizing amine group via reductive amination gave the desired design in moderate to very good yields. Molecular modeling studies of these compounds predicted possible binding modes into the active site of dopamine receptor D2.

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.

Borinic Acid Mediated Hydrosilylations: Reductions of Carbonyl Derivatives

4-Fluoro-2-chlorophenylborinic acid acts as a precatalyst in the presence of phenylsilane for the facile reduction of ketones, aldehydes and imines. Notably, synergistic mediation of a tertiary amine was found essential to trigger silicon to boron hydride transfer to generate a key amine–diarylhydroborane Lewis complex.

“Inverse” Frustrated Lewis Pairs: An Inverse FLP Approach to the Catalytic Metal Free Hydrogenation of Ketones

For the first time have boron-containing weak Lewis acids been demonstrated to be active components of Frustrated Lewis Pair (FLP) catalysts in the hydrogenation of ketones to alcohols. Combining the organosuperbase (pyrr)3P=NtBu with the Lewis acid 9-(4-CF3-C6H4)-BBN generated an “inverse” FLP catalyst capable of hydrogenating a range of aliphatic and aromatic ketones including N-, O- and S-functionalized substrates and bio-mass derived ethyl levulinate. Initial computational and experimental studies indicate the mechanism of catalytic hydrogenation with “inverse” FLPs to be different from conventional FLP catalysts that contain strong Lewis acids such as B(C6F5)3.

Stable and Inert Cobalt Catalysts for Highly Selective and Practical Hydrogenation of C≡N and C=O Bonds

Novel heterogeneous cobalt-based catalysts have been prepared by pyrolysis of cobalt complexes with nitrogen ligands on different inorganic supports. The activity and selectivity of the resulting materials in the hydrogenation of nitriles and carbonyl compounds is strongly influenced by the modification of the support and the nitrogen-containing ligand. The optimal catalyst system ([Co(OAc)2/Phenα-Al2O3]-800 = Cat. E) allows for efficient reduction of both aromatic and aliphatic nitriles including industrially relevant dinitriles to primary amines under mild conditions. The generality and practicability of this system is further demonstrated in the hydrogenation of diverse aliphatic, aromatic, and heterocyclic ketones as well as aldehydes, which are readily reduced to the corresponding alcohols.

Selective Catalytic Hydrogenations of Nitriles, Ketones, and Aldehydes by Well-Defined Manganese Pincer Complexes

Hydrogenations constitute fundamental processes in organic chemistry and allow for atom-efficient and clean functional group transformations. In fact, the selective reduction of nitriles, ketones, and aldehydes with molecular hydrogen permits access to a green synthesis of valuable amines and alcohols. Despite more than a century of developments in homogeneous and heterogeneous catalysis, efforts toward the creation of new useful and broadly applicable catalyst systems are ongoing. Recently, Earth-abundant metals have attracted significant interest in this area. In the present study, we describe for the first time specific molecular-defined manganese complexes that allow for the hydrogenation of various polar functional groups. Under optimal conditions, we achieve good functional group tolerance, and industrially important substrates, e.g., for the flavor and fragrance industry, are selectively reduced.

Synthesis of 3H, 2H4 and 14C-SCH 417690 (Vicriviroc)

Vicriviroc or SCH 417690 is a potent and selective antagonist of the CCR5 receptor. CCR5 receptor antagonists have the potential for the treatment of HIV infections. Four distinct isotopically labelled forms of SCH 417690 were synthesized. Low specific activity [3H]SCH 417690 was prepared for a preliminary absorption, distribution, metabolism and excretion evaluation of the compound and [14C]SCH 417690 for more definitive absorption, distribution, metabolism and excretion work, including an absorption, metabolism and excretion study in man. In addition, high specific activity [3H]SCH 417690 was prepared for CCR5 receptor binding work and [2H4]SCH 417690 was prepared as an internal standard for a liquid chromatography-mass spectrometry bioanalytical method. The paper discusses the synthesis of four isotopically labelled forms of SCH 417690.