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mL). kk The aqueous layer was extracted with EtOAc (3 x 100 mL) and the extracts were
combined, dried over MgSO4 and concentrated under vacuum to afford the desired carboxylic
acid, which was then dissolved in CH2Cl2 (70 mL). To this solution were then added, HOBt
(0.407 g 3.10 mmol), EDCI (0.579 g, 3.10 mmol), DMAP (0.738 g, 6.20 mmol) and gycine
methylester·HCl (0.379 g, 3.10 mmol) at rt. The reaction was stirred at rt for 90 min, and then
diluted with CH2Cl2 (150 mL). The solution was washed with water (50 mL), sat’d aq. NH4Cl (2
x 50 mL), then dried over MgSO4, filtered and concentrated under vacuum. Purification of the
crude residue by flash chromatography (hexanes-EtOAc, 4 : 1 to 1 : 1, v/v) afforded 154a (0.710
g, 65%) which was used in the next step without additional purification.
1 H NMR (300 MHz, CDCl3): δ 7.40-7.35 (m, 1H), 7.28-7.15 (m, 5H), 6.96 (bs, 1H), 6.27 (dd, J
= 17.1, 10.7 Hz, 1H), 6.14 (q, J = 7.5 Hz, 1H), 5.88 (s, 1H), 5.45 (dd, J = 17.1, 1.6 Hz, 1H), 5.21
(dd, J = 10.8, 1.63 Hz, 1H), 4.16 (dd, J = 18.0, 5.9 Hz, 1H), 3.93 (dd, J = 18.0, 5.2 Hz, 1H), 3.72
(s, 3H), 3.41 (d, J = 13.4 Hz, 1H), 3.16 (d, J = 13.4 Hz, 1H), 2.12 (d, J = 7.4 Hz, 3H); 13 C NMR
(75 MHz, CDCl3): δ 171.8, 170.2, 165.8, 138.9, 137.4, 134.5, 133.6, 130.8, 128.1, 127.1, 125.1,
120.9, 118.2, 65.8, 52.3, 44.9, 41.4, 16.0; IR (thin film): ν 3304, 2951, 1745, 1669, 1635, 1209
cm -1 ; MS m/z (%) 354 (9), 263 (40), 238 (100), 174 (31), 91 (90); EI-HRMS calc’d for
C20H22N2O4 m/z [M] + 354.1580; found 354.1582.
kk In certain cases the homogeneous solution separated into two layers upon addition of LiOH and saponification did
not proceed to completion. In these cases it is advantageous to add additional amount of water under vigorous
stirring until the reaction mixture becomes homogeneous again.
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