40431-64-9

Usage

Uses

Treatment of attention deficit/hyperactivity disorder.

Definition

ChEBI: A methyl phenyl(piperidin-2-yl)acetate in which both stereocentres have R configuration. It is the active enantiomer in the racemic drug methylphenidate.

Upstream product

• 67-56-1 methanol 
• 19395-41-6 Ritalinic acid 
• 110-89-4 piperidine 
• 22979-35-7 Methyl phenyldiazoacetate 
• 460356-15-4 (Z)-3-Amino-7-methanesulfonyloxy-2-phenyl-hept-2-enoic acid methyl ester 
• 75844-69-8 t-butyl piperidinecarboxylate 
• 2427-16-9 5-hydroxy-pentanenitrile 
• 7251-52-7 2-phenyl-2-(pyridin-2-yl)acetamide 
• 5005-36-7 phenyl-pyridin-2-yl-acetonitrile 
• 113-45-1 METHYLPHENIDATE 
• 298-59-9 methylphenidate hydrochloride 
• 194041-29-7 D-threo-methylphenidate di-p-toluoyl-D-tartaric acid salt 
• 160707-37-9 d-threo-2-phenyl-2-(piperidine-2-yl)acetamide 
• 109-09-1 2-chloropyridine 

Downstream Products

• 19262-68-1 dexmethylphenidate hydrochloride 
• 298-59-9 methylphenidate hydrochloride 

Relevant academic research and scientific papers

An efficient large scale resolution of (±)-threo-methylphenidate hydrochloride (Ritalin hydrochloride)

An efficient and large scale preparation of (2R,2'R)-(+)-threo-methylphenidate hydrochloride (3) by the resolution of (±)-threo-methylphenidate hydrochloride (1) salt with O,O'-dibenzoyl-D-(+)-tartaric acid in the presence of 4-methylmorpholine is described.

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.

α-C-H Bond Functionalization of Unprotected Alicyclic Amines: Lewis-Acid-Promoted Addition of Enolates to Transient Imines

Enolizable cyclic imines, obtained in situ from their corresponding lithium amides by oxidation with simple ketone oxidants, are readily alkylated with a range of enolates to provide mono- and polycyclic β-aminoketones in a single operation, including the natural product (±)-myrtine. Nitrile anions also serve as competent nucleophiles in these transformations, which are promoted by BF3 etherate. β-Aminoesters derived from ester enolates can be converted to the corresponding β-lactams.

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.

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.

ABUSE DETERRENT AND ANTI-DOSE DUMPING PHARMACEUTICAL SALTS USEFUL FOR THE TREATMENT OF ATTENTION DEFICIT/HYPERACTIVITY DISORDER

A pharmaceutical composition comprising a drug substance consisting essentially of a pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound wherein the amine containing pharmaceutical active compound is selected from the group consisting of racemic or single isomer ritalinic acid or phenethylamine derivatives and the drug substance has a physical form selected from amorphous and polymorphic.

Studies on the Eschenmoser coupling reaction and insights on its mechanism. Application in the synthesis of Norallosedamine and other alkaloids

The conditions of the Eschenmoser coupling reaction were studied. The formation of the α-thioiminium ion was achieved faster in the presence of an additive (NaI) and dry chloroform as the preferred solvent. The developed conditions were used for the second part of the reaction (the sulfur extrusion itself). The present protocol avoids the formation of byproducts, which were previously described as a major drawback to be overcome. Electrospray ionization tandem mass spectrometry was used to characterize some aspects (intermediates) of the first step of the reaction mechanism. Some reduction conditions were properly tested and the selected conditions were applied to the synthesis of the natural alkaloid Norallosedamine and other derivatives.

Process of enantiomeric resolution of D,L-(+_)-threo-methylphenidate

A process for preparing the d-threo isomer of methylphenidate hydrochloride which includes (i) resolving a racemic mixture of racemic threo-methylphenidate hydrochloride with a less than stoichiometric amount of tertiary amine base to obtain a methylphenidate-chiral acid salt, (ii) basifying the methylphenidate-chiral acid salt to obtain methylphenidate free base, and (iii) converting the methylphenidate free base into d-threo-methylphenidate hydrochloride.

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.