(S)-2-[3-ethoxycarbonyl-2-(4-methoxy-phenoxy)-allylamino]-4-methyl-pentanoic acid methyl ester → (S)-2-[4-(4-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-2-[3-ethoxycarbonyl-2-(4-methoxy-phenoxy)-allylamino]-4-methyl-pentanoic acid methyl ester (0.83 g, 2.51 mmol) in tetrahydrofuran (10 mL) was heated to 160° C. in a high pressure reaction vessel for 24 h. At this time, the reaction was cooled to 25° C. and was concentrated in vacuo. Purification by Analogix flash chromatography (40 g, 20-30% ethyl acetate/hexanes) afforded (S)-2-[4-(4-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester (0.39 g, 46%) as a yellow oil: HR-ES-MS m/z calculated for C18H23NO5 [M+H]+ 334.1649, observed 334.1649; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.87 (d, J=6.6 Hz, 3H), 0.92 (d, J=6.6 Hz, 3H), 1.39-1.53 (m, 1H), 1.53-1.68 (m, 1H), 1.68-1.87 (m, 1H), 3.65 (s, 3H), 3.77 (s, 3H), 4.13 (d, J=18.1 Hz, 1H), 4.20 (d, J=18.1 Hz, 1H), 4.72 (dd, J=11.3, 4.4 Hz, 1H), 4.77 (s, 1H), 7.00 (d, J=9.1 Hz, 2H), 7.23 (d, J=9.1 Hz, 2H).

Provenance & Evidence