Reaction Steps
A catalytic quantity of DMF (2 drops) was added to a stirred solution of 108 (10 g, 38.9 mmol) and oxalyl chloride (5.87 g, 46.2 mmol) in dry CHCl2 (100 mL) under a nitrogen atmosphere. The reaction mixture was allowed to stir overnight, and the product was used directly in the next stage of the reaction. The newly formed acid chloride was added dropwise to a stirred solution of pyrrolidinemethanol (3.92 g, 38.8 mmol) and anhydrous triethylamine (12.4 mL, 9.8 g, 97.0 mmol) in anhydrous DCM (50 mL) at 0° C. under nitrogen. Once the addition was complete, the reaction mixture was left to warm to room temperature and left to stir overnight. The reaction mixture was washed with 1N HCl (100 mL), water (100 mL), and brine (2×100 mL). The combined organic layers were dried (MgSO4) and the solvent was removed in vacuo to afford 109 (12.1 g, 91%) as a pale yellow oil: Rf=0.39 (silica, EtOAc); [α]21.9D+135° (c=0.1, DCM); IR (neat) 3400, 3105, 2947, 2878, 1652, 1568, 1538, 1455, 1348, 1250, 1195, 1115, 975, 922, 849, 822, 792, 758, 733, 646 cm−1; 1H NMR (270 MHz, CDCl3) δ 7.59 (1H, s), 4.46 (2H, d, J=2.93 Hz), 4.07 (3H, s), 4.03 (3H, s), 4.01 (3H, s), 3.89 (3%, t), 3.45-3.29 (2H, m), 2.24-2.17 (2H, m), 2.00-1.84 (2H, m); 13C NMR (67.8 MHz, CDCl3, rotamers) δ 165.7, 165.1, 153.3, 149.2, 148.1, 138.8, 122.5, 104.1, 66.4, 65.5, 62.4, 62.3, 61.3, 56.6, 49.2, 49.0, 28.7 24.3; MS (EI) m/z 341 (M+1), 324, 309, 293, 277, 264, 254.
