881-95-8

Basic information

• Product Name: DL-M-O-METHYLEPINEPHRINE HYDROCHLORIDE
• Synonyms: (+-)-4-hydroxy-3-methoxy-alpha-((methylamino)methyl)benzenemethanolhydrochlo;3-methoxy-adrenalinhydrochloride;4-hydroxy-3-methoxy-alpha-((methylamino)methyl)-benzenemethanohydrochlorid;alpha-((methylamino)methyl)-vanillylalcohohydrochloride;4-HYDROXY-3-METHOXY-ALPHA-[METHYLAMINOMETHYL]BENZENE-METHANOL HYDROCHLORIDE;4-HYDROXY-3-METHOXY-ALPHA-(METHYLAMINOMETHYL)BENZYL ALCOHOL HYDROCHLORIDE;METANEPHRINE (HCL);METANEPHRINE HYDROCHLORIDE
• CAS NO: 881-95-8
• Molecular Formula: C₁₀H₁₅NO₃*ClH
• Molecular Weight: 233.69
• EINECS: 212-922-2
• Product Categories: Standards - 13C & 2H for GC-Mass Spectrometry;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 881-95-8.mol
• Article Data: 1

Chemical Properties

• Melting Point: 180-182?C
• Boiling Point: 378.8 °C at 760 mmHg
• Flash Point: 182.9 °C
• Appearance: white to off-white/powder
• Density: 1.320 g/cm3
• Storage Temp.: -20°C Freezer
• Solubility: H2O: soluble
• CAS DataBase Reference: DL-M-O-METHYLEPINEPHRINE HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: DL-M-O-METHYLEPINEPHRINE HYDROCHLORIDE(881-95-8)
• EPA Substance Registry System: DL-M-O-METHYLEPINEPHRINE HYDROCHLORIDE(881-95-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: DA4798000
• Hazardous Substances Data: 881-95-8(Hazardous Substances Data)

Usage

Chemical Properties

Off-White to Pale Yellow Solid

Uses

A metabolite of Epinephrine (E588585). A naturraly occurring derivative of Epinephrine, found in urine and in certain tissues.

Biochem/physiol Actions

Metanephrine is an endogenous metabolite of ephinephrine, formed by catechol-O-methyl transferase activity. It is best known as a biomarker for cancers, as levels of free metanephrine are used to diagnose pheochromocytoma. Metanephrine was previously thought to be biologically inactive, but it is a more potent agonist at Trace amine associated receptor TAAR1 than either epinephrine or norepinephrine. Trace amine associated receptors (TAARs) are recently discovered GPCRs that are activated by endogenous trace amines (tyramine, tryptamine, synephrine, octopamine, β-phenylethylamine), which are chemically similar to monoaminergic neurotransmitters (epinephrine, norepinephrine, dopamine). Trace amines and TAARs are expressed in brain and are implicated in modulation of monoaminergic neurotransmission.

InChI:InChI=1/C10H15NO3.ClH/c1-11-6-9(13)7-3-4-8(12)10(5-7)14-2;/h3-5,9,11-13H,6H2,1-2H3;1H

Synthetic route

1-(4-hydroxy-3-methoxy-phenyl)-2-methylamino-ethanone (91012-60-1) → dl-metanephrine hydrochloride (881-95-8)

Conditions	Yield
With hydrogenchloride; hydrogen; palladium In ethanol for 6h;	72%

4-acetyl-2-methoxyphenyl acetate (54771-60-7) → dl-metanephrine hydrochloride (881-95-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: SeO2 / dioxane; H2O / 4 h / Heating 2: 61 percent / H2 / Raney Ni / ethanol; H2O / 0.33 h 3: 72 percent / conc. aq. HCl, H2 / Pd black / ethanol / 6 h View Scheme

3-methoxy-4-hydroxyphenylglyoxal (32025-66-4) → dl-metanephrine hydrochloride (881-95-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 61 percent / H2 / Raney Ni / ethanol; H2O / 0.33 h 2: 72 percent / conc. aq. HCl, H2 / Pd black / ethanol / 6 h View Scheme

maleic anhydride (108-31-6) + dl-metanephrine hydrochloride (881-95-8) → N-hemimaleoyl-DL-metanephrine

Conditions	Yield
With triethylamine In methanol for 0.0833333h; Ambient temperature;

methanol-toluene + N-(4-chlorobenzyl)-9-(chloromethyl)-1-methyl-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide (556025-47-9) + dl-metanephrine hydrochloride (881-95-8) → rac N-(4-chlorobenzyl)-9-{[[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)ethyl](methyl)amino]methyl}-1-methyl-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide (556025-17-3)

Conditions	Yield
In N,N-dimethyl-formamide

N-(4-chlorobenzyl)-6-(chloromethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide (281652-09-3) + dl-metanephrine hydrochloride (881-95-8) → N-(4-chlorobenzyl)-6-{[[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)ethyl](methyl)amino]methyl}-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide

3-(pyridin-3-yl)acrylic acid (1126-74-5) + pivaloyl chloride (3282-30-2) + dl-metanephrine hydrochloride (881-95-8) → (E)-N-[2-hydroxy-2-(3-methoxy-4-hydroxyphenyl)ethyl]-N-methyl-3-(pyridin-3-yl)-2-propenoic acid amide (219965-69-2)

Conditions	Yield
With triethylamine In N-methyl-acetamide; water	1.41 g (80%)

Upstream product

• 32025-66-4 3-methoxy-4-hydroxyphenylglyoxal 
• 91012-60-1 1-(4-hydroxy-3-methoxy-phenyl)-2-methylamino-ethanone 
• 54771-60-7 4-acetyl-2-methoxyphenyl acetate 

Downstream Products

• 219965-69-2 (E)-N-[2-hydroxy-2-(3-methoxy-4-hydroxyphenyl)ethyl]-N-methyl-3-(pyridin-3-yl)-2-propenoic acid amide 

Relevant articles and documents

SYNTHESIS OF 3-O-METHYLATED DERIVATIVES OF CATECHOLAMINES

3-O-Methylated catecholamines, used in the radioenzyme method for the analysis of catecholamines in blood, were synthesized. The optimum conditions for the production of both the intermediate and the final products were determined. By the use of tetrabutylammonium bromide in the condensation of nitromethane with O-benzylvanilin it is possible to obtain a high yield of 1-(3-methoxy-4-benzyloxyphenyl)-2-nitroethanol. The latter is easily transformed at a palladium catalyst into methylnoradrenaline by reduction with ammonium formate. The reduction of 1-(3-methoxy-4-benzyloxyphenyl)-2-nitroethylene with hydrogen or its donors at a palladium catalyst takes place significantly more readily in the presence of ferric chloride.