265994-88-5

Basic information

• Product Name: (-)-(R)-2-[2-(2,6-dimethylphenoxy)-1-methylethyl]-1H-isoindole-1,3(2H)-dione
• Synonyms: (-)-(R)-2-[2-(2,6-dimethylphenoxy)-1-methylethyl]-1H-isoindole-1,3(2H)-dione
• CAS NO: 265994-88-5
• Molecular Weight: 309.365
• Mol File: 265994-88-5.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: (-)-(R)-2-[2-(2,6-dimethylphenoxy)-1-methylethyl]-1H-isoindole-1,3(2H)-dione(CAS DataBase Reference)
• NIST Chemistry Reference: (-)-(R)-2-[2-(2,6-dimethylphenoxy)-1-methylethyl]-1H-isoindole-1,3(2H)-dione(265994-88-5)
• EPA Substance Registry System: (-)-(R)-2-[2-(2,6-dimethylphenoxy)-1-methylethyl]-1H-isoindole-1,3(2H)-dione(265994-88-5)

Safety Data

• Hazardous Substances Data: 265994-88-5(Hazardous Substances Data)

Upstream product

• 576-26-1 2.6-dimethylphenol 
• 73323-91-8 (1'R)-N-(1'-hydroxyethyl-2'-methyl)-1H-isoindole-1,3(2H)-dione 
• 136918-14-4 phthalimide 
• 85-44-9 phthalic anhydride 

Downstream Products

• 31828-71-4 (R)-mexiletine 

Relevant articles and documents

Asymmetric hydrolytic kinetic resolution with recyclable macrocyclic CoIII-salen complexes: A practical strategy in the preparation of (R)-mexiletine and (S)-propranolol

A chiral cobalt(III) complex (1 e) was synthesized by the interaction of cobalt(II) acetate and ferrocenium hexafluorophosphate with a chiral dinuclear macrocyclic salen ligand that was derived from 1R,2R-(-)-1,2-diaminocyclohexane with trigol bis-aldehyde. A variety of epoxides and glycidyl ethers were suitable substrates for the reaction with water in the presence of chiral macrocyclic salen complex 1 e at room temperature to afford chiral epoxides and diols by hydrolytic kinetic resolution (HKR). Excellent yields (47 % with respect to the epoxides, 53 % with respect to the diols) and high enantioselectivity (ee>99 % for the epoxides, up to 96 % for the diols) were achieved in 2.5-16 h. The CoIII macrocyclic salen complex (1 e) maintained its performance on a multigram scale and was expediently recycled a number of times. We further extended our study of chiral epoxides that were synthesized by using HKR to the synthesis of chiral drug molecules (R)-mexiletine and (S)-propranolol.

Stereospecific synthesis of mexiletine and related compounds: Mitsunobu versus Williamson reaction

Mexiletine [1-(2,6-dimethylphenoxy)-2-propanamine], a chiral, orally effective antiarrhythmic agent, and several analogues substituted on either the stereogenic centre or the xylyloxy moiety, were prepared in both, highly enriched, optically active forms. According to the 'chiral pool' approach, the appropriate amino alcohols, protected as the corresponding phthalimide derivatives, were condensed with the desired phenols under either Mitsunobu (method A) or Williamson (method B) conditions. Generally, method A provided the most efficient route, both in terms of yields and number of steps necessary. Only when an isopropyl group was present on the stereogenic centre, i.e. when 2-amino-3-methylbutanol was used as the starting alcohol, method B proved to be the only available route, method A giving no product other than the starting phthalimide derivative. Regardless of the method used, enantiomeric excesses ranged from 91 to 99%. Given the availability of both variously substituted phenols and optically active amino alcohols, the two methods described herein, taken together, may serve as a versatile approach, useful to meet the needs of new chiral, optically active mexiletine analogues, possibly endowed with higher potency in exerting a use-dependent block on sodium channels and/or more resistant to biotransformations. Copyright (C) 2000 Elsevier Science Ltd.