L-Methyl-4-phenylpiperidine

Meperidine Meperidine, the ethyl ester of l-methyl-4-phenylpiperidine-4-carboxyhc acid (3.1.39), is a synthetic opioid analgesic. Its synthesis is accomphshed by the alkylation of benzyl cyanide using Af,Al-fcix-(2-chlorethyl)-iV-methylamine in the presence of sodium amide, which forms l-methyl-4-phenyl-4-cyanopiperidine (3.1.38), and its subsequent acidic ethanolysis into meperidine [30-32]. 

Pethidine-Intermediate-C, l-methyl-4-phenylpiperidine-4-car-boxylic acid. 

A very important contribution to analgesia was made in 1939 by the introduction of ethyl l-methyl-4-phenylpiperidine-4-carboxylate hydrochloride, currently known as meperidine in the U.S.A. (8). Eisleb and Schaumann introduced this substance from the I.G. Farbenindustrie laboratories into Germany as an antispasmodic under the name of dolantin. While an excellent analgesic, there was no need to introduce meperidine under the multiplicity of synonyms now confusing the pharmacology of analgesics ... 

Methoxyphenoxy)methyl] -l-methyl-4-phenylpiperidine Hydrochloride (FG 4963) in Biological Fluids Using Com-pettion for Adsorption to Glass J. Chromatogr. 133(1) 147-152 (1977) ... 

Meperidine hydrochloride (l-methyl-4-carbethoxy-4-phenylpiperidine), also known as Demerol, is an important narcotic and analgesic. It is not made from piperidine, but rather by ring-closure reactions of appropriate precursors,... 

From 4.1 parts DL-4-(aminomethyl)-l-[2-(l,4-benzodioxanyl)methyl]-4-phenylpiperidine dihydrochloride, the free base is liberated in the usual manner and extracted with chloroform. The organic layer is separated, dried and evaporated. The DL-4-(aminomethyl)-l-[2-(l,4-benzodioxanyl)methyl]-4-phenylpiperidine obtained is dissolved in 128 parts anhydrous chloroform. This solution is cooled to 5°C and there is added dropwise a solution of 1.6 parts acetylchloride in 7 parts anhydrous chloroform (exothermic reaction). The reaction mixture is stirred over night at room temperature and then alkalized with about 25 parts sodium hydroxide 20% at a temperature of 20°C. The aqueous layer is separated and extracted twice with chloroform. The combined organic layers are washed with water, dried over magnesium sulfate, filtered and evaporated. The oily residue is dissolved in a mixture of 40 parts acetone and 20 parts diisopropyl ether and evaporated again. The solid residue is triturated in diisopropylether, yielding DL-4-(N-acetylaminomethyl)-l-[2-(l,4-benzodioxanyl)-methyl]-4-phenylpiperidine melting point 140°-141.1°C, as a white microcrystalline powder. 

Evaporation of an acetic acid solution of l-methyl-3,4-dibromo-4-phenylpiperidine hydrobromide (130) (obtained from 127 by addition of bromine in acetic acid) was unexpectedly accompanied by dehydro-bromination, with the formation of l-methyl-4-phenyl-5-bromo-3-piperideine hydrobromide (131).115... 

Casy and McErlane have reported synthetic and stereochemical studies on the l,2-dimethyl-4-phenylpiperidin-4-ols (357), and on the 3-methyl-4-phenylpiperidines (358). By comparison of the i.r. spectra of [ N]- and... 

A mixture of 750 grams of l-methyl-3-benzoyl-4-hydroxy-4-phenylpiperidine and 2,500 cc of 48% hydrobromic acid is refluxed for about 20 minutes. It is then poured into 8 liters of water. An oily precipitate appears which on standing crystallizes. It is filtered and crystallized from about 3.5 liters of alcohol. 2-Methyl-9-phenyl-2,3-dihydrel-pyridindene hydrobromide, MP 201°-203°C, is obtained. 

Triflic acid catalyzes the arylation of Af-methyl-l,2,3,6-tetrahydropyridine 227 to give 4-phenylpiperidine 229 (Scheme 59) <2001TL5821>. The reaction is believed to proceed by initial formation of a 1,4-dication 228, which forms in preference to the 1,3-dication 231. When yV-methyl-5-phenyl-l,2,3,6-tetrahydropyridine 230 is arylated under the same conditions, 3,3-diphenylpiperidine 232 is formed as the sole product showing the stabilization of the 1,3-dication intermediate 231 by the tertiary 5-position. Intramolecular arylation of 2- and 6-benzyl-substituted 1,2,3,6-tetrahydropyridines can also be catalyzed by triflic acid <20050L4309>. 

METHYLCARBAMOYLOXY)PHENYL)TRIMETHA L-ARSONIUM IODIDE see GD900 1-METHYL-4-CARBETHOXY-4-PHENYLPIPERIDINE HYDROCHLORIDE see DAM700 METHYLCARBINOL see EFUOOO METHYL CARBITOL see DJGOOO METHYL-4-CARBOMETHOXY BENZOATE see DUEOOO... 

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