(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

HRID 19068Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:27])[C@@H:4]([NH:9][CH2:10][C:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)=[CH:12][C:13](OCC)=[O:14])[CH2:5][CH:6]([CH3:8])[CH3:7]>O1CCCC1>[CH3:1][O:2][C:3](=[O:27])[C@@H:4]([N:9]1[CH2:10][C:11]([O:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[CH:12][C:13]1=[O:14])[CH2:5][CH:6]([CH3:8])[CH3:7]

Participants

Conditions

Temperature: 25 °C

Procedure

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).

Workup

concentrationwas concentrated in vacuo
customPurification by Analogix flash chromatography (40 g, 20-30% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-b0963a3adbbe436697e9b3de3cae3c5a
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07741327B2

Reaction notes

Loading…