298-59-9

Usage

Uses

1. Used in Pharmaceutical Industry:
Methylphenidate hydrochloride is used as a psychostimulant for the treatment of attention-deficit hyperactivity disorder (ADHD). It works by blocking dopamine and norepinephrine transporters, as well as facilitating NMDA-receptor mediated synaptic transmission through σ1 receptors via PLC/PKC signaling. This interaction with the σ1 receptor has been suggested to underlie methylphenidate's considerable abuse potential and potential psychiatric side effects.
2. Used in Narcolepsy Treatment:
Methylphenidate hydrochloride is also used as a potent CNS stimulant for the treatment of narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and sudden episodes of sleep.
3. Used in Anti-Inflammatory Applications:
Although not explicitly mentioned in the provided materials, Methylphenidate hydrochloride has been studied for its potential anti-inflammatory properties, which could be useful in various medical applications.
4. Used in Forensic and Biological Research:
Methylphenidate hydrochloride is used in forensic and biological research applications, likely due to its complex structure and multiple modes of action, which can provide valuable insights into the mechanisms of CNS stimulants and their effects on the brain.

Therapeutic Function

Psychostimulant

Air & Water Reactions

Water soluble.

Reactivity Profile

Methylphenidate hydrochloride is incompatible with alkalis and solutions of barbiturates . Undergoes typical ester hydrolysis in aqueous solutions at 176°F.

Fire Hazard

Flash point data for Methylphenidate hydrochloride are not available; however, Methylphenidate hydrochloride is probably combustible.

Biological Activity

Psychomotor stimulant. Inhibitor of dopamine and noradrenalin transporters that increases the extracellular concentration of dopamine and noradrenalin. Increases locomotor activity in vivo .

Veterinary Drugs and Treatments

Methylphenidate may be useful for treating cataplexy/narcolepsy or hyperactivity in dogs.

InChI:InChI=1/C14H19NO2/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3/t12-,13+/m0/s1

Upstream product

• 67-56-1 methanol 
• 1076192-92-1 threo-ritalinic acid 
• 113-45-1 dl-threo-methylphenidate 
• 113-45-1 methyl (R*)-2-phenyl-2-((S*)-piperidin-2-yl)acetate 
• 1076192-92-1 2-phenyl-2-(piperidin-2-yl)acetic acid 
• 2629-91-6 7-phenyl-1-aza-bicyclo[4.2.0]octan-8-one 
• 81929-14-8 N-(2,2,2-trichloroethylidene)prop-2-en-1-amine 
• 103-80-0 phenylacetyl chloride 
• 113-45-1 METHYLPHENIDATE 
• 19395-41-6 Ritalinic acid 

Downstream Products

• 19130-92-8 (+/-)-threo-ritalinic acid hydrochloride 
• 851764-84-6 (+/-)-threo-ethylphenidate hydrochloride 
• 42510-61-2 (+/-)-threo-Ritalinol 
• 252979-89-8 l-threo-methylphenidate / dibenzoyl L-tartaric acid 

Relevant academic research and scientific papers

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.

AN IMPROVED PROCESS FOR THE PREPARATION OF DEXMETHYL PHENIDATE HYDROCHLORIDE

Disclosed herein a process for the preparation of highly pure dexmethylphenidate hydrochloride (Formula-I) which comprises the steps of neutralization of dl- threomethylphenidate hydrochloride to dl-threo methylphenidate; subsequent resolution of dl-threo methylphenidate using amino acid or its derivatives as chiral resolution agent to yield dexmethylphenidate salt; hydrolysis of the salt and further conversion of dexmethylphenidate into its hydrochloride salt.

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).

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.

An improved manufacturing process for methylphenidate and intermediates thereof

The present invention discloses selective and complete reduction of pyridine ring in a biaryl system comprising α-substituted or non-substituted benzene ringand relates more specifically, not exclusively, for the manufacture of methylphenidate, which is used for treatment of Attention Deficit Hyperactive Disorder (ADHD) and also acts as central nervous system stimulant, by using palladium/C in a solvent such as C1-C4 alcohols in presence of molar quantities of organic and/or inorganic acids.

Manufacturing process for methyl phenidate and intermediates thereof

The present invention discloses selective and complete reduction of pyridine ring in a biaryl system comprising ∝-substituted or nonsubstituted benzene ring and relates more specifically, not exclusively, for the manufacture of methylphenidate, which is used for treatment of Attention Deficit Hyperactive Disorder (ADHD) and also acts as central nervous system stimulant, by using palladium/C in a solvent such as C1-C4 alcohols in presence of molar quantities of organic and/or inorganic acids.