318279-38-8

Basic information

• Product Name: (+/-)-TRANS-4-(FLUOROPHENYL)-3-HYDROXYMETHYL-1-METHYLPIPERIDINE
• Synonyms: (+/-)-TRANS-4-(4-FLUOROPHENYL)-3-HYDROXYMETHYL-1-METHYLPIPERIDINE;TRANS(+/-)-4-(4-FLUOROPHENYL)-3-HYDROXYMETHYL-1-METHYLPIPERIDINE;TRANS-4-(4-FLUOROPHENYL)-3-HYDROXYMETHYL-1-METHYLPIPERIDINE;(+/-)-TRANS-4-(FLUOROPHENYL)-3-HYDROXYMETHYL-1-METHYLPIPERIDINE;TRANS-4-(P-FLUOROPHENYL)-3-HYDROXYMETHYL-1-METHYLPIPERIDINE;(3R-,4S)-REL-4-(4-FLUOROPHENYL)-1-METHYL-3-PIPERIDINE METHANOL;4-(4-fluorophenyl)-1-methyl-3-Piperidinemethanol
• CAS NO: 318279-38-8
• Molecular Formula: C₁₃H₁₈FNO
• Molecular Weight: 223.29
• Mol File: 318279-38-8.mol
• Article Data: 11

Chemical Properties

• Boiling Point: 300.283 °C at 760 mmHg
• Flash Point: 135.406 °C
• Appearance: /
• Density: 1.092 g/cm³
• PKA: 14.93±0.10(Predicted)
• CAS DataBase Reference: (+/-)-TRANS-4-(FLUOROPHENYL)-3-HYDROXYMETHYL-1-METHYLPIPERIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: (+/-)-TRANS-4-(FLUOROPHENYL)-3-HYDROXYMETHYL-1-METHYLPIPERIDINE(318279-38-8)
• EPA Substance Registry System: (+/-)-TRANS-4-(FLUOROPHENYL)-3-HYDROXYMETHYL-1-METHYLPIPERIDINE(318279-38-8)

Safety Data

• Hazardous Substances Data: 318279-38-8(Hazardous Substances Data)

Usage

General Description

The chemical (±)-trans-4-(fluorophenyl)-3-hydroxymethyl-1-methylpiperidine is a synthetic compound with a piperidine core structure. It is a chiral molecule, meaning it has two enantiomers that are mirror images of each other, designated as (+) and (-). (+/-)-TRANS-4-(FLUOROPHENYL)-3-HYDROXYMETHYL-1-METHYLPIPERIDINE has a fluorophenyl group attached to the piperidine ring and a hydroxymethyl group at the para position of the phenyl ring. It is a potential intermediate or building block in organic synthesis and may have potential applications in medicinal chemistry and drug development due to the presence of the piperidine moiety, which is a common structural motif in many pharmaceutical compounds. Its stereochemistry and functional groups could also make it useful as a ligand in chemical and biological research.

Synthetic route

trans 3-ethoxycarbonyl-4-(4'-fluorophenyl)-N-methyl-piperidine-2,6-dione (202534-94-9) + sulfuric acid (7664-93-9) → trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methyl piperidine (318279-38-8)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran	91%
With sodium hydroxide In tetrahydrofuran	91%

trans 3-ethoxycarbonyl-4-(4'-fluorophenyl)-N-methyl-piperidine-2,6-dione (202534-94-9) → trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methyl piperidine (318279-38-8)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran; dichloromethane; toluene at -15 - 40℃; for 2.5h; Solvent; Inert atmosphere;	75%
With sodium hydroxide In tetrahydrofuran; water	65%

aqueous formaldehyde (formalin) + (3RS,4SR)-[4-(4-fluoro-phenyl)-piperidin-3-yl]-methanol (216690-19-6) → trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methyl piperidine (318279-38-8)

Conditions	Yield
aluminum nickel In methanol; water

4-(4-fluorophenyl)-1-methyl-piperidine-3-carboxylic acid methyl ester (315197-82-1) → trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methyl piperidine (318279-38-8)

Conditions	Yield
Stage #1: 4-(4-fluorophenyl)-1-methyl-piperidine-3-carboxylic acid methyl ester With sodium bis(2-methoxyethoxy)aluminium dihydride In toluene at 27 - 40℃; for 0.25h; Stage #2: With hydrogenchloride In water; toluene at 12℃; for 0.25h;

4-p-fluorophenyl-3-formyl-1-methylpyridinium bromide + ethanol (64-17-5) + sodium hydrogencarbonate (144-55-8) → trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methyl piperidine (318279-38-8)

Conditions	Yield
platinum (IV) oxide In dichloromethane

N,N-dimethyl-ethanamine (598-56-1) + p-toluenesulfonyl chloride (98-59-9) + (3S,4R)-trans-4-(4-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine (105812-81-5) + trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methyl piperidine (318279-38-8) → (3S,4R)-trans-4-(4-fluorophenyl)-1-methyl-3-p-toluenesulphonyloxymethyl-piperidine (317323-77-6)

Conditions	Yield
With sodium hydroxide In dichloromethane

Upstream product

• 64-17-5 ethanol 
• 144-55-8 sodium hydrogencarbonate 
• 315197-82-1 4-(4-fluorophenyl)-1-methyl-piperidine-3-carboxylic acid methyl ester 
• 202534-94-9 trans 3-ethoxycarbonyl-4-(4'-fluorophenyl)-N-methyl-piperidine-2,6-dione 
• 7664-93-9 sulfuric acid 
• 216690-19-6 (3RS,4SR)-[4-(4-fluoro-phenyl)-piperidin-3-yl]-methanol 

Downstream Products

• 317323-77-6 ((3S,4R)-4-(4-fluorophenyl)-1-methylpiperidin-3-yl)methyl 4-methylbenzenesulfonate 

Relevant articles and documents

AN IMPROVED PROCESS FOR MINIMISING THE FORMATION OF DEHALOGENATED BYPRODUCTS

The present invention provides an improved process for preparation of organic compounds represented by Formula-Z; wherein effectively minimising the formation of dehalogenated by-products is achieved. In the process, the reduction is carried out using suitable reducing agent; more preferably Lithium Aluminium Hydride (LAH) in a solvent system, wherein at least one of the solvent is selected from halogenated solvents, which acts as co-solvent. The process of the present invention is useful for minimising of the formation of dehalogenated by-products during synthesis of various active pharmaceutical ingredients such as Paroxetine Hydrochloride, Cinacalcet, Eletriptan and Asenapine.

Process for preparing (+)trans-4-p-fluorophenyl-3-hydroxymethyl-1-methylpiperidine

The present invention relates to a process for preparing (±)-trans-4-p-fluorophenyl-3-hyroxymethyl-1-methylpiperdine of formula (I). The present invention also relates to novel intermediates of the formula (IX) and (IX′) methods for preparing said intermediates and the use of said compounds for preparing Paroxetine and Omiloxetine.

Novel process

A process for the preparation of a 4-aryl-3-oxymethyl-piperidine of structure (1) in which R is hydrogen or an alkyl, arylalkyl, allyl, acyl, carbonyloxyalkyl, carbonyloxyaryl, or carbonyloxyalkylaryl group, and Y is a hydrogen atom or an optionally substituted alkyl, arylalkyl, or aryl group, from a carboxy derivative of structure (2) where A is oxygen or sulphar, X is one or more of hydrogen, or a readily reducible group, Z represents either a hydrogen atom or an OY′ group in which Y′ is independently selected from the same groups as Y, and the broken line circle indicates bonding, appropriate to a tetrahydropyridine, dihydropyridine, pyridine, or piperidine ring said process comprising (a) when Y is a hydrogen atom, reducing the compound of structure (2), or (b) when Y is other than a hydrogen atom (i) forming an ether from the alcohol product of step (a), (ii) etherifying the aldehyde compound of structure (2) in which Z is hydrogen, or (iii) reducing the ester compound of structure (2) in which Z is OY′.