Further study of oxazolidines derived from mefloquine and arenealdehydes: diastereoisomers and polymorphs

Authors: Pinheiro, Alessandra C.; Kaiser, Carlos R.; LourenÇo, Maria C.S.; de Souza, Marcus V.N.; Wardell, Solange M.S.V.; Wardell, James L. Goncalves, R.S.B.; De Souza, M.V.N.; Wardell, S.M.S.V.; Wardell, J.L.


Abstract

The reaction between racemic erythro [(R*,S*)-2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanol] and 2-formyl-5-nitrothiene in toluene generates a reaction mixture containing two diastereoisomers of 4-[3-(5-nitrothien-2-yl)-hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline, 6, – namely (2S*,3R*,4S*5R*)-6 (6a) and (2R*,3S*,4S*,5R*)-6 (6b) in a ratio of 5:1 as indicated by 1H NMR spectroscopy (using the 1,3-oxazolidine ring numbering scheme for the chiral centres). Isolation of each product from the mefloquine/2-formyl-5-nitrothiene reaction mixture was achieved by fractional crystallisation of an ethanol solution, but not by column chromatography on silica, which led to the destruction of the minor product, 6b. A second polymorphic form, [monoclinic, P21/c] of (2S*,3R*,4S*,5R*)-4-[3-(2-hydroxyphenyl-hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline (monoclinic-7) has been isolated from MeOH solution: the previously reported orthorhombic form, space group Fdd2, had been isolated from an ethanolic solution.
Keywords: diasteromers; mefloquine derivatives, oxazolidines; polymorphs Document Type: Research Article DOI: http://dx.doi.org/10.1515/zkri-2015-1858 Publication date: 1 de Janeiro de 2016 [:en]

Abstract

The reaction between racemic erythro [(R*,S*)-2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanol] and 2-formyl-5-nitrothiene in toluene generates a reaction mixture containing two diastereoisomers of 4-[3-(5-nitrothien-2-yl)-hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline, 6, – namely (2S*,3R*,4S*5R*)-6 (6a) and (2R*,3S*,4S*,5R*)-6 (6b) in a ratio of 5:1 as indicated by 1H NMR spectroscopy (using the 1,3-oxazolidine ring numbering scheme for the chiral centres). Isolation of each product from the mefloquine/2-formyl-5-nitrothiene reaction mixture was achieved by fractional crystallisation of an ethanol solution, but not by column chromatography on silica, which led to the destruction of the minor product, 6b. A second polymorphic form, [monoclinic, P21/c] of (2S*,3R*,4S*,5R*)-4-[3-(2-hydroxyphenyl-hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline (monoclinic-7) has been isolated from MeOH solution: the previously reported orthorhombic form, space group Fdd2, had been isolated from an ethanolic solution.


Keywords: diasteromers; mefloquine derivatives, oxazolidines; polymorphs Document Type: Research Article DOI: http://dx.doi.org/10.1515/zkri-2015-1858 Publication date: 1 de Janeiro de 2016 [:]

Compartilhar publicação

Facebook
Twitter
Email
LinkedIn
WhatsApp

Deixe seu comentário

Compartilhar

Sobre a SSCDT

Nosso grupo de pesquisa está situado em Farmanguinhos e atualmente é o maior laboratório farmacêutico oficial vinculado ao Ministério da Saúde. Farmanguinhos produz mais de um bilhão de medicamentos por ano para os programas estratégicos do Governo Federal, além de atender demandas emergenciais no Brasil e no exterior.

posts Recentes