29419-95-2

Basic information

• Product Name: L-METHYLPHENIDATE
• Synonyms: L-METHYLPHENIDATE;(2S)-2-Phenyl-2-[(S)-2-piperidinyl]acetic acid methyl ester;(αS,2S)-α-Phenyl-2α-piperidineacetic acid methyl ester;(αS,2S)-α-Phenylpiperidine-2α-acetic acid methyl ester;[(αS,2S)-α-Phenyl-2α-piperidineacetic acid]methyl ester;l-threo-Methylphenidate;L-Ritalin hydrochloride;(S)-methyl 2-phenyl-2-((S)-piperidin-2-yl)acetate hydrochloride
• CAS NO: 29419-95-2
• Molecular Formula: C₁₄H₁₉NO₂*ClH
• Molecular Weight: 269.7671
• Mol File: 29419-95-2.mol

Chemical Properties

• Melting Point: 219-221 °C
• Appearance: white/
• Solubility: H2O: soluble32mg/mL
• CAS DataBase Reference: L-METHYLPHENIDATE(CAS DataBase Reference)
• NIST Chemistry Reference: L-METHYLPHENIDATE(29419-95-2)
• EPA Substance Registry System: L-METHYLPHENIDATE(29419-95-2)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• Hazardous Substances Data: 29419-95-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
L-METHYLPHENIDATE is used as a CNS stimulant for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Its stimulant properties help improve focus, attention, and impulse control in individuals with ADHD, while also promoting wakefulness in those suffering from narcolepsy.
Used in Research and Development:
In the field of scientific research, L-METHYLPHENIDATE serves as a valuable compound for studying the effects of enantiomers on the human body. Its less potent nature compared to other enantiomers allows researchers to investigate the differences in pharmacological activity and potential therapeutic applications.
Used in Drug Regulation and Control:
As a controlled substance, L-METHYLPHENIDATE plays a crucial role in the regulation and control of drug distribution and use. Its classification helps ensure that it is prescribed and used responsibly, minimizing the risk of misuse and addiction.

Biochem/physiol Actions

Central nervous system stimulant. Less potent enantiomer.

Upstream product

• 67-56-1 methanol 
• 1076192-92-1 threo-ritalinic acid 
• 298-59-9 methylphenidate hydrochloride 
• 1076192-92-1 2-phenyl-2-(piperidin-2-yl)acetic acid 
• 81929-14-8 N-(2,2,2-trichloroethylidene)prop-2-en-1-amine 
• 103-80-0 phenylacetyl chloride 
• 203056-33-1 1-[(2S)-N-(tert-butyloxycarbonyl)piperidin-2-yl]-1-(4-methoxyphenyl)ethene 
• 203056-25-1 1-[(2R)-N-(tert-butyloxycarbonyl)piperidin-2-yl]-1-(4-methoxyphenyl)ethene 
• 203056-34-2 (S,S)-2-[N-(tert-butyloxycarbonyl)piperidin-2-yl]-2-phenylethanol 
• 203056-32-0 1-[(2S)-N-(tert-butyloxycarbonyl)piperidin-2-yl]-1-(4-bromophenyl)ethene 
• 203056-22-8 1-[(2R)-N-(tert-butyloxycarbonyl)piperidin-2-yl]-1-(4-bromophenyl)ethene 
• 22979-35-7 Methyl phenyldiazoacetate 
• 75844-69-8 t-butyl piperidinecarboxylate 
• 2629-91-6 7-phenyl-1-aza-bicyclo[4.2.0]octan-8-one 

Downstream Products

• 1076192-92-1 2-phenyl-2-(piperidin-2-yl)acetic acid 
• 1076192-92-1 d-Ritalinic acid 
• 40572-71-2 threo-(-)-Methylphenidate 
• 40431-64-9 dexmethylphenidate 
• 252979-89-8 l-threo-methylphenidate / dibenzoyl L-tartaric acid 
• 113-45-1 dl-threo-methylphenidate 

Relevant articles and documents

The asymmetric synthesis of (S,S)-methylphenidate hydrochloride via ring-opening of an enantiopure aziridinium intermediate with phenylmagnesium bromide

The key step in our synthetic strategy towards (S,S)-methylphenidate hydrochloride employs the ring-opening of an in situ formed aziridinium intermediate. Treatment of an α-hydroxy-β-amino ester with methanesulfonic anhydride promoted aziridinium formation and the subsequent addition of phenylmagnesium bromide resulted in stereospecific and regioselective ring-opening to give the corresponding α-phenyl-β-amino ester with overall retention of configuration. Subsequent functional group manipulation followed by N-deprotection and cyclisation generated the piperidine ring within the target compound, and transesterification gave (S,S)-methylphenidate hydrochloride, in only 8 steps from 1,5-pentanediol, in 15% overall yield. These results demonstrate the synthetic utility of enantiopure aziridinium intermediates as substrates for the generation of stereodefined C–C bonds, and crucially this methodology provides access to α-substituted-β-amino ester substrates that are not accessible via enolate alkylation chemistry. The strategy reported herein is potentially applicable to all possible stereoisomers of methylphenidate as well as differentially substituted analogues.

Changing stereoselectivity and regioselectivity in copper(i)-catalyzed 5-: Exo cyclization by chelation and rigidity in aminoalkyl radicals: Synthesis towards diverse bioactive N-heterocycles

The work reveals that a chelate-Type interaction in the transition state of a β-Aminoalkyl radical in a copper(i)-catalyzed 5-exo-Trig radical cyclization step changes the usual stereochemistry of the NH-pyrrolidine ring predicted by the Beckwith-Houk transition state model. In contrast, the rigidity in the fused β-Aminoalkyl radical changes the Baldwin's predicted 5-exo to 6-endo cyclization mode, preferentially forming a piperidine ring over a pyrrolidine ring via a geometrically constrained transition state. The resultant diverse NH-pyrrolidines, pyrrolines and piperidines are sources of the bioactive natural product roseophilin and the drug Ritalin among others.

IMPROVEMENTS IN OR RELATING TO ORGANIC MATERIAL

The invention provides a method for the preparation of an intermediate for use in synthesizing a lower alkyl phenidate compound of formula (I), wherein each R1 independently represents an optionally substituted aryl, heteroaryl, alkyl, cycloalkyl, alkoxy, aryloxy, acyl, carboxyl, hydroxyl, halogen, amino, nitro, sulfo or sulfhydryl group, R2 represents a hydrogen atom or a lower alkyl group, n represents an integer from 1 to 5 and m represents an integer from 1 to 3 or a pharmaceutically acceptable salt thereof; which method comprises the steps of: (a) flowing a tosylhydrazone compound of formula (IV), wherein R1, n and m are as defined above in relation to the methylphenidate of formula (I), an organic base and an organic solvent into a fluidic network; and (b) reacting the tosylhydrazone compound of formula (IV) and the base in the fluidic network under thermal and/or photochemical conditions to form a transient diazoamide compound of formula (V), wherein R1, n and m are as defined above in relation to the methylphenidate of formula (I).

Concise and facile synthesis of (R,R)-dexmethylphenidate hydrochloride and its three stereoisomers

A new and concise route is reported for the first time for the preparation of four stereoisomers of dexmethylphenidate hydrochloride starting from a single reactant, 2-benzyolpyridine, through an eight-step reaction process, which includes hydrogenation,

PROCESS FOR THE PREPARATION OF METHYLPHENIDATE AND PHARMACEUTICAL SALTS THEREOF

The present invention is directed to an improved process for the preparation of methylphenidate, stereoisomer, mixture of stereoisomers and pharmaceutically acceptable salts thereof, more particularly, the sulfate and hydrochloride salts of methylphenidate, di-threo-methylphenidate and dex-methylphenidate. Methods of removing or reducing the amount of impurities from the above described process are also disclosed.

LOW-TEMPERATURE SYNTHESIS OF METHYLPHENIDATE HYDROCHLORIDE

The present invention describes a process for the preparation of methylphenidate hydrochloride. The process involves the esterification of ritalinic acid and methanol in the presence of an acid catalyst at a low temperature. The process may optionally involve the addition of an orthoester.

PROCESS FOR PREPARING METHYL PHENIDATE HYDROCHLORIDE

Disclosed herein is a process for the preparation of methyl phenidate hydrochloride (Formula I), comprising the steps of; hydrolyzing α-phenyl-α-pipyridyl acetamide (Formula II) in presence of mineral acid at reflux temperature and subsequent neutralization to yield threo -α-phenyl-α-pipyridyl-2-acetic acid (Formula III) which in presence of acidic catalyst reacts with methanol followed by treatment with alcoholic hydrochloride solution produces methyl phenidate hydrochloride.

Synthesis of Methylphenidate and Analogs Thereof

A synthetic process for the preparation of amino acid esters such as methylphenidate and analogs thereof is disclosed. The process involves reacting an amino acid such as α-phenyl-α-(2-piperidinyl)acetic acid or an analog thereof with an alcohol such as methanol in the presence of an acid and a water sequestrant such as trimethyl orthoacetate. In some embodiments, the water sequestrant is added to the reaction mixture after an initial period of esterification and then the reaction is allowed to continue. The α-phenyl-α-(2-piperidinyl)acetic acid methyl ester or analog thereof is then isolated from the reaction mixture. In one variation of the process, the supernatant liquid may be recycled in subsequent runs to increase yield and product purity.

Method to separate stereoisomers

A method to resolve the stereoisomers of an optically active compound comprising an amine moiety. The method provides a mixture comprising two stereoisomers of a compound comprising a amine moiety. The method supplies l-fenchyloxyacetic acid, treats the mixture of stereoisomers with that l-fenchyloxyacetic acid, and collects one of those two stereoisomers having greater than a 99 percent enantiomeric excess.

Process for the preparation of threo-methylphenidate hydrochloride

The present invention provides a process for the preparation of threo-methylphenidate hydrochloride. According to a preferred embodiment, the process comprises the following steps: (a) contacting 1-(phenylglyoxylyl)piperidine arenesulfonylhydrazone of the formula wherein Ar denotes an aryl group, where the aryl group may be substituted by a C1-C6 alkyl, halo or nitro group; with an inorganic base in the presence of a water immiscible organic solvent and a phase transfer catalyst to obtain (R*,R*)-enriched 7-phenyl-1-azabicyclo[4.2.0]octan-8-one of the formula: (b) reacting the (R*,R*)-enriched 7-phenyl-1-azabicyclo[4.2.0]octan-8-one prepared in step (a) with a solution of hydrogen chloride in methanol to obtain threo-enriched methylphenidate hydrochloride; (c) crystallizing the threo-enriched methylphenidate hydrochloride prepared in step (b) to give the desired threo-methylphenidate hydrochloride. Preferably, the threo-methylphenidate hydrochloride produced by the process of the present invention contains no more than 1% of the erythro-isomer.