25772-81-0Relevant academic research and scientific papers
Preparation method of methocarbamol beta isomer
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Paragraph 0029-0032, (2017/08/27)
The invention provides a preparation method of a methocarbamol beta isomer. According to the preparation method, a 2-((Methoxyphenoxy)methyl)ethylene oxide compound 1 is taken as a starting raw material and is sequentially subjected to chlorination, ester
Process for the Preparation of Ranolazine
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Paragraph 0031; 0032, (2013/04/13)
A process for the preparation of ranolazine comprises the step of condensing N-(2,6-dimethylphenyl)-1-piperazinyl acetamide with a compound of formula (I) to obtain ranolazine, in which X is chlorine or bromine Ranolazine is prepared by condensing ring-opening halide which replaces epoxide in this process.
An efficient synthesis of 1-(2-Methoxyphenoxy)-2,3-epoxypropane: Key intermediate of β-adrenoblockers
Madivada, Lokeswara Rao,Anumala, Raghupathi Reddy,Gilla, Goverdhan,Kagga, Mukkanti,Bandichhor, Rakeshwar
, p. 1660 - 1664 (2013/02/25)
An efficient process for the preparation of 1-(2-methoxyphenoxy)-2,3- epoxypropane, a key intermediate for the synthesis of ranolazine is described.
Efficient synthesis of 8-methoxy-3,4-dihydro-2H-1-benzopyran-3-ol
Shindikar,Viswanathan
experimental part, p. 1141 - 1145 (2011/05/05)
The article reports a practical, simple, and inexpensive procedure for the synthesis of 8-methoxy-3,4-dihydro-2H-1-benzopyran-3-ol (1). 2-Methoxy phenol on treatment offers the oxirane compound, which undergoes ring cleavage under acidic conditions to give a chlorohydrin, which on acylation and cyclization in the presence of stannic chloride followed by hydrolysis of the acetyl group, yields the desired compound (1).
Improvement and simplification of synthesis of 3-aryloxy-1,2-epoxypropanes using solvent-free conditions and microwave irradiations. Relation with medium effects and reaction mechanism
Pchelka, Beata K.,Loupy, Andre,Petit, Alain
, p. 10968 - 10979 (2007/10/03)
Some 3-aryloxy-1,2-epoxypropanes, interesting as potential synthons in β-adrenergic receptor antagonists preparation, were obtained in excellent yields (65-96% within 2-17 min) by microwave activation (monomode system) using solid-liquid solvent-free phase transfer catalysis (PTC). The best results for the O-alkylation of some phenols with epichlorohydrin were obtained using TBAB and NaOH/K2CO3 (1:4 mol/mol) as phase transfer catalyst and more acceptable basic system, respectively. These new procedure is compared with classical methods. Significant specific microwave effect (non-purely thermal) was evidenced in all cases. They were discussed in terms of reaction medium and mechanism, taking into account the variations in polarity of the systems.
Cyclization-Activated Prodrugs: N-(Substituted 2-hydroxyphenyl and 2-hydroxypropyl)carbamates Based on Ring-Opened Derivatives of Active Benzoxazolones and Oxazolidinones as Mutual Prodrugs of Acetaminophen
Vigroux, Alain,Bergon, Michel,Zedde, Chantal
, p. 3983 - 3994 (2007/10/03)
N-(Substituted 2-hydroxyphenyl)- and N-(substituted 2-hydroxypropyl)carbamates based on masked active benzoxazolones (model A) and oxazolidinones (model B), respectively, were synthesized and evaluated as potential drug delivery systems.A series of alkyl and aryl N-(5-chloro-2-hydroxyphenyl)carbamates 1 related to model A was prepared.These are open drugs of the skeletal muscle relaxant chlorzoxazone.The corresponding 4-acetamidophenyl ester named chloracetamol is a mutual prodrug of chloroxazone and acetaminophen.Chlorzacetamol and two other mutual prodrugs of active bezoxazolones and acetaminophen were obtained in a two-step process via condensation of 4-acetamidophenyl 1,2,2,2-tetrachloroethyl carbonate with the appropiate anilines.Based on model B, two mutual prodrugs of acetaminophen and active oxazolidinones (metaxalone and mephenoxalone) were similarly obtained using the appropiate amines.All the carbamate prodrugs prepared were found to release the parent drugs in aqueous (pH 6-11) and plasma (pH 7.4) media.The detailed mechanistic study of prodrugs 1 carried out in aqueous medium at 37 deg C shows a change in the Broensted-type relationship log t1/2 vs pKa of the leaving groups ROH: log t1/2 = 0.46pKa - 3.55 for aryl and trihalogenoethyl esters and log t1/2 = 1.46pKa - 16.03 for alkyl esters.This change is consistent with a cyclization mechanism involving a change in the rate-limiting step from formation of a cyclic tetrahedral intermediate (step k1) to departure of the leaving group ROH (step k2) when the leaving group ability decreases.This mechanism occurs for all the prodrugs related to model A.Regeneration of the parent drugs from mutual prodrugs related to model B takes place by means of a rate-limiting elimination-addition reaction (E1cB mechanism).This affords acetaminophen and the corresponding 2-hydroxypropyl isocyanate intermediates which cyclize at any pH to the corresponding oxazolidinone drugs.As opposed to model A, the rates of hydrolysis of mutual prodrugs of model B clearly exhibit a catalytic role of the plasma.It is concluded from the plasma studies that the carbamate substrates can be enzymatically transformed into potent electrophiles, i.e., isocyanates.In the case of the present study, the prodrugs are 2-hydroxycarbamates for which the propinquity of the hydroxyl residue and the isocyanate group enforces a cyclization reaction.This mechanistic particularity precludes their potential toxicity in terms of potent electrophiles capable of modifying critical macromolecules.
