Reaction Steps
The benzyl ester C4 (30 g, 79.9 mmol) was suspended in dry DCM (300 mL) with stirring in a round-bottomed flask equipped with a drying tube. Oxalyl chloride (11.16 g, 7.66 mL, 1.1 eq) was added followed by a few drops of DMF. The mixture was stirred overnight at room temperature. Triethylamine (17.75 g, 24.45 mL, 2.2 eq), +(S)-pyrrolidine methanol (8.876 g, 8.66 mL, 1.1 eq) were dissolved in dry DCM (150 mL) under nitrogen. The solution was cooled below −30° C. The acid chloride solution was added dropwise over 6 h maintaining the temperature below −30° C. It was then left to stir overnight at room temperature. The resulting solution was extracted with 1N HCl (2×200 mL), twice with water, once with brine. It was dried with magnesium sulfate and concentrated in vacuo to give a yellow/brown oil which solidified on standing. (quantitative yield). It was used in the next step without further purification. 1H NMR (DMSO-d6) Mixture of rotamers in a 35/65 ratio. δ 7.75 (m, 1H), 7.34 (m, 5H), 7.16 (s, 0.35H), 7.09 (s, 0.65H), 5.16 (s, 2H), 4.36 (m, 2H), 4.10 (m, 0.65H), 3.91 (s, 3H), 3.73-3.61 (m, 1H), 3.46-3.37 (m, 2.35H), 3.16-3.08 (m, 2H), 2.94-2.90 (m, 2H), 1.98-1.72 (m, 4H); 13C NMR (100 MHz, DMSO-d6) δ 170.4, 165.5, 154.0, 147.2, 136.9, 136.0, 128.6, 128.3, 128.2, 128.1, 127.9, 127.7, 109.9, 108.3, 79.1, 65.6, 64.8, 64.7, 61.7, 60.6, 59.9, 58.6, 56.6, 48.4, 45.7, 33.7, 27.4, 27.0, 23.4, 21.6; IR (CHCl3) 1735, 1618, 1577, 1519, 1453, 1427, 1383, 1332, 1275, 1218, 1171, 1058, 871, 750, 698, 649 cm−1; MS (ES+) m/z (relative intensity) 459.13 ([M+H]+, 100); [α]25D=−532° (c=0.12, CHCl3).
