Preparation of an N-sec-alkyl 2,6-disubstituted aniline: a key intermediate in the divergent synthesis of S-Metolachlor metabolites
| Autor: | Timothy J. Carlin, Bruce P. McKillican, William J. Eberle, Alan John Dowling, David A. Hunt, Jeffrey A. Key, Sameer Tyagi, Christopher D. Cook, Moses G. Gichinga |
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| Rok vydání: | 2016 |
| Předmět: |
chemistry.chemical_classification
010405 organic chemistry Metabolite Organic Chemistry Substituent Alkylation 010402 general chemistry 01 natural sciences Biochemistry 0104 chemical sciences chemistry.chemical_compound Aniline chemistry Drug Discovery Side chain Organic chemistry Metolachlor Divergent synthesis Alkyl |
| Zdroj: | Tetrahedron Letters. 57:5363-5367 |
| ISSN: | 0040-4039 |
| DOI: | 10.1016/j.tetlet.2016.10.077 |
| Popis: | A simple method to prepare a 2,6-disubstituted aniline containing a N-sec-alkyl group and a carbonyl on one ortho substituent is reported. This method was used to accomplish the first synthesis of side chain oxidized ethylsulfonic acid (ESA) and oxanilic acid (OXA) metabolites of S-Metolachlor (S-Moc) herbicide. The 2,6-disubstituted aniline functionality was installed by a Sugasawa reaction of readily available ortho-toluidine. The N-sec alkyl group was introduced by a Mitsunobu alkylation of the nosyl-activated 2-acetyl-6-methyl-substituted aniline. This crucial step enabled access to the key 2,6-disubstituted aniline intermediate which was used in the divergent synthesis of S-Moc metabolites. A bioinspired synthesis of the keto-ESA metabolite was achieved in one step from the hydroxyl-ESA metabolite using a ruthenium-catalyzed oxidation. Download : Download full-size image |
| Databáze: | OpenAIRE |
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