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Synthesis 2009(21): 3649-3653  
DOI: 10.1055/s-0029-1216989
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Simple and Efficient Synthesis of N-Substituted Cyclohex-3-enamines

Mónica Álvarez-Pérez*, José Marco-Contelles*
Laboratorio de Radicales Libres y Química Computacional, IQOG (CSIC), C/ Juan de la Cierva 3, 28006 Madrid, Spain
Fax: +34(91)3944103; e-Mail: monicaap@quim.ucm.es; e-Mail: iqoc21@iqog.csic.es;
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Publication History

Received 26 April 2009
Publication Date:
03 September 2009 (online)

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Abstract

A straightforward preparation of N-substituted cyclohex-3-enamines starting from the commercially available trans-4-aminocyclohexanol hydrochloride is described. Cyclohex-3-enamino-functionalized compounds have proven to be interesting intermediates in medicinal chemistry. The method here described is cheaper, more scalable and tolerant of a broader variety of functional groups than those found in the literature for this type of compound.

Key words

eliminations - olefinations - medicinal chemistry - amines - nitrogenated cyclohexenes

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1

New address: Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040-Madrid, Spain.

15

See experimental section.

19

A preliminary attempt to perform both steps in one pot gave rise to 20% of 2c and 32% of 3c, which is quite promising but requires further optimization.

20

Starting from 7 g of 1c, 5.6 g of 2c was obtained after purification.

21

The moderate yield obtained starting from compound 1f might be due to its low solubility in CH2Cl2 and/or the ease of hydrolysis of the trifluoroacetamide group.