Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides

Gydo van der Heijden, Timo B. van Schaik, Valentinos Mouarrawis, Martin J.M. de Wit, Christophe M.L.Vande Velde, Eelco Ruijter, Romano V.A. Orru

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

An efficient Ugi-type three-component reaction (U-3CR) for the synthesis of pipecolic amides is reported. The U-3CR between electronically diverse isocyanides, carboxylic acids and 4-substituted Δ1-piperideines proceeds in a highly diastereoselective fashion. The Δ1-piperideines are obtained by NCS-mediated oxidation of the corresponding 4-substituted piperidines, which in turn are generated by an efficient two-step procedure involving the alkylation of 4-picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U-3CR, in combination with the convertible isocyanide 2-bromo-6-isocyanopyridine, in the synthesis of the anticoagulant argatroban.

Original languageEnglish
JournalEuropean Journal of Organic Chemistry
DOIs
Publication statusPublished - 1 Jan 2019

Fingerprint

Cyanides
Amides
amides
Picolines
Piperidines
anticoagulants
piperidine
alkylation
Alkylation
synthesis
Carboxylic Acids
carboxylic acids
Anticoagulants
Hydrogenation
hydrogenation
pyridines
Oxidation
oxidation
rings
pyridine

Keywords

  • Argatroban
  • Multicomponent reactions
  • Pharmaceuticals
  • Pipecolic amides
  • Stereoselectivity

Cite this

van der Heijden, Gydo ; van Schaik, Timo B. ; Mouarrawis, Valentinos ; de Wit, Martin J.M. ; Velde, Christophe M.L.Vande ; Ruijter, Eelco ; Orru, Romano V.A. / Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides. In: European Journal of Organic Chemistry. 2019.
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keywords = "Argatroban, Multicomponent reactions, Pharmaceuticals, Pipecolic amides, Stereoselectivity",
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Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides. / van der Heijden, Gydo; van Schaik, Timo B.; Mouarrawis, Valentinos; de Wit, Martin J.M.; Velde, Christophe M.L.Vande; Ruijter, Eelco; Orru, Romano V.A.

In: European Journal of Organic Chemistry, 01.01.2019.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - van Schaik, Timo B.

AU - Mouarrawis, Valentinos

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AU - Velde, Christophe M.L.Vande

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AU - Orru, Romano V.A.

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KW - Stereoselectivity

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