19262-68-1

Usage

Uses

Used in Pharmaceutical Industry:
D-THREO-METHYLPHENIDATE HYDROCHLORIDE is used as a controlled substance for the treatment of attention deficit hyperactivity disorder (ADHD) in children. It is the more potent isomer of Methylphenidate and has shown to improve ADHD symptoms to a similar extent as racemic methylphenidate at half the usual dose. The drug is well-tolerated, with common adverse events being mild in severity.
D-THREO-METHYLPHENIDATE HYDROCHLORIDE is used as a CNS stimulant for its longer duration of action compared to the racemic form, as measured by a behavioral scale at 6 hours post dosing. It is metabolized to d-α-phenyl-piperidine acetic acid, its main urinary metabolite with negligible pharmacological activity. In vitro studies have shown that dexmethylphenidate does not inhibit cytochrome P450 isozymes.
Brand Name:
Focalin (Novartis) is the brand name for D-THREO-METHYLPHENIDATE HYDROCHLORIDE. It is recommended to be administered twice daily with an interval of at least 4 hours between doses. Stimulant medications, including dexmethylphenidate, have been the first-line pharmacological therapy for children with ADHD for over sixty years, demonstrating effectiveness in roughly 70% of patients.

Originator

Celgene (USA)

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-/m1/s1

Upstream product

• 67-56-1 methanol 
• 1076192-92-1 threo-ritalinic acid 
• 237419-31-7 (R)-2-((R)-Methoxycarbonyl-phenyl-methyl)-piperidine-1-carboxylic acid tert-butyl ester 
• 1076192-92-1 d-Ritalinic acid 
• 220858-76-4 1-(tert-butyloxycarbonyl)-α-(R)-phenyl-2-(R)-piperidineacetic acid 
• 22979-35-7 Methyl phenyldiazoacetate 
• 75844-69-8 t-butyl piperidinecarboxylate 
• 258825-18-2 methyl (2R,2'R)-2-phenyl-2-(N-methoxycarbonyl-2'-piperidyl)acetate 
• 40431-64-9 dexmethylphenidate 
• 298-59-9 methylphenidate hydrochloride 
• 113-45-1 METHYLPHENIDATE 
• 741705-70-4 d-threo-ritalinic acid hydrochloride 
• 80-11-5 N-methyl-N-nitrosotoluene-p-sulfonamide 
• 1076192-92-1 2-phenyl-2-(piperidin-2-yl)acetic acid 

Downstream Products

• 252979-89-8 l-threo-methylphenidate / dibenzoyl L-tartaric acid 
• 851764-84-6 (+/-)-threo-ethylphenidate hydrochloride 
• 19130-92-8 (+/-)-threo-ritalinic acid hydrochloride 
• 1076192-92-1 2-phenyl-2-(piperidin-2-yl)acetic acid 
• 113-45-1 dl-threo-methylphenidate 

Relevant academic research and scientific papers

Palladium-Catalyzed Enantioselective C(sp3)-H/C(sp3)-H Umpolung Coupling of N-Allylimine and α-Aryl Ketones

Asymmetric functionalization of the C(sp3)-H bond is an attractive yet challenging strategy to achieve versatile bond-forming events, enabling the precise assembly of molecular complexity with minimal manipulation of functional groups. Here, we report an asymmetric C(sp3)-H/C(sp3)-H umpolung coupling of N-allylimine and coordinating α-aryl carbonyls by using chiral phosphoramidite-palladium catalysis. A wide variety of α-heteroaryl ketones and 2-acylimidazoles are nicely tolerated to open a convenient and tunable avenue for efficient synthesis of enantioenriched β-amino-γ,δ-unsaturated carbonyl derivatives with high levels of regio- and stereoselectivities, capable of providing a key intermediate for asymmetric synthesis of Focalin. This protocol showcases an umpolung reactivity of the N-allylimines through a concerted proton and two-electron transfer process to cleave the allylic C-H bond, effectively complementing established methodology for allylic C-H functionalization. An inner-sphere allylation pathway for both α-heteroaryl carbonyls and 2-acylimidazoles to attack the π-allylpalladium species is suggested by computational studies and experimental facts, wherein the nitrogen coordination to the palladium center enables the preference of branched regioselectivity.

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.

Preparation method and application of tartaric acid derivative

, The product is prepared by reacting. tartaric acid and oxalyl chloride as raw materials under the action of an acid-binding agent and D - can be used as a chiral resolution agent for chiral medicine, the preparation method of the product is simple, in a polar solvent . and the chiral resolution is, The method is high, purity.

Preparation method of dexmethylphenidate

The invention relates to a new synthetic route of dexmethylphenidate. Methyl phenylacetate serves as a raw material, and the dexmethylphenidate is synthesized at high yield through four steps of an amidation reaction, a diazotization reaction, a cyclization reaction and a rearrangement reaction. The preparation method of the dexmethylphenidate is high in yield, low in cost, environmentally friendly, easy to operate and suitable for industrialization.

Methylphenidate, right pai methyl ester preparation method, intermediate and preparation method

The invention discloses preparation methods of methylphenidate and dexmethylphenidate, intermediates and preparation methods of the intermediates. The invention provides the preparation method of the methylphenidate, wherein the preparation method is any one of the following methods: a first method comprises the following steps of in a solvent, carrying out an amino protecting group removal reaction of a compound 4 with an amino de-protection reagent, and thus obtaining the methylphenidate 5; a second method comprises the following steps of under the action of an alkali, carrying out an intramolecular nucleophilic substitution reaction of a compound 11 to obtain the methylphenidate 5; and a third method comprises the following steps of in a closed system, in a solvent, under a palladium on carbon or palladium carbon hydroxide catalytic condition, carrying out a reaction of a compound 9 with hydrogen, to obtain the methylphenidate 5. The synthesis method has the advantages of short steps, cheap and easily obtained raw materials, high product yield, good chiral purity, low production cost, and good atomic economy, and is suitable for industrialized production.

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,

An Improved and Efficient Process for the Production of Highly Pure Dexmethylphenidate Hydrochloride

The present work describes an efficient and commercially viable process for the synthesis of dexmethylphenidate hydrochloride (1), a mild nervous system stimulant. The overall yield is 23% with ~99.9% purity (including seven chemical steps). Formation and control of possible impurities are also described in this report.

Preparation method of dexmethylphenidate hydrochloride

The invention discloses a preparation method of dexmethylphenidate hydrochloride. The preparation method comprises a step: in a solvent, carrying out salt forming reactions between inorganic acid salts or organic acid salts of compounds represented by the

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.