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DOI: 10.1055/s-0029-1219533
An Efficient Procedure for the Synthesis of Morpholin-2-one-3-carboxamide Derivatives in Good Diastereoselectivity by the Ugi Reaction
Publication History
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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References and Notes
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.