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Synlett 2010(6): 897-900  
DOI: 10.1055/s-0029-1219533
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient Procedure for the Synthesis of Morpholin-2-one-3-carboxamide Derivatives in Good Diastereoselectivity by the Ugi Reaction

Deguang Zhu, Ruijiao Chen, Haibo Liang, Sheng Li, Li Pan, Xiaochuan Chen*
Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China
Fax: +86(28)85413712; e-Mail: chenxc@scu.edu.cn;
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Publication History

Received 17 November 2009
Publication Date:
18 February 2010 (online)

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Abstract

A series of 5-substituted morpholin-2-one-3-carbox­amide derivatives were efficiently synthesized by a Ugi three-­component reaction involving chiral 5,6-dihydro[1,4]oxazin-2-one substrates, isocyanides and carboxylic acids. The newly formed chiral center in the product was obtained in good diastereoselectivity.

Key words

Ugi reaction - isonitrile - multicomponent reaction - ­diastereoselectivity - morpholin-2-one

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7

General procedure for the synthesis of 4: To a solution of 1 were added, successively, acid 3 and isocyanide 2 under inert atmosphere. The resulting mixture was stirred at room temperature until completion (TLC), and concentrated in vacuo. The residue was purified by flash chromatography on silica gel column to give product 4

14

4a: [a]D ²8 +4 (c 0.5, CHCl3). IR (neat): 3337, 2963, 2932, 1752, 1666, 1539, 1463, 1391, 1289, 1108 cm-¹. ¹H NMR (400 MHz, CDCl3): d (two rotamers) = 7.66-7.61 (m, 4 H), 7.46-7.40 (m, 6 H), 5.98 (s, 1 H), 4.95 (s, 0.8 H), 4.82 (dd, J = 2.7, 11.5 Hz, 1 H), 4.76 (s, 0.2 H), 4.71 (dd, J = 1.3, 11.4 Hz, 0.8 H), 4.58 (m, 0.2 H), 4.47 (dd, J = 2.8, 12.0 Hz, 0.2 H), 3.93 (m, 0.8 H), 3.86 (dd, J = 4.0, 9.6 Hz, 0.2 H), 3.70 (t, J = 10.6 Hz, 0.8 H), 3.59 (dd, J = 5.3, 10.7 Hz, 0.8 H), 3.52 (t, J = 9.6 Hz, 0.2 H), 1.89 (s, 0.6 H), 1.82 (s, 2.4 H), 1.36 (s, 1.8 H), 1.33 (s, 7.2 H), 1.06 (s, 7.2 H),
1.05 (s, 1.8 H) ppm. ¹³C NMR (100 MHz, CDCl3): d (two rotamers) = 169.9, 169.8, 165.7, 163.3, 162.2, 162.1, 135.4, 135.3, 132.5, 131.9, 130.2, 130.1, 127.9, 127.7, 127.6, 66.7, 65.8, 62.7, 61.0, 60.7, 60.2, 52.9, 52.6, 52.2, 50.0, 29.6, 28.3, 26.6, 21.1, 20.4, 19.0 ppm. HRMS: m/z [M + Na]+ calcd for C28H38N2O5Si: 533.2448; found: 533.2437.