Reaction Steps
To a solution of N-CBZ-cis-4-hydroxy-L-proline ethyl ester (6.4 g, 22 mmol) and anhydrous pyridine (5.3 mL, 5.2 g, 65 mmol) in CHCl3 (35 mL) was added p-toluenesulfonyl chloride (8.3 g, 44 mmol) in one portion. After stirring at room temperature for 7 days, the reaction was diluted with CH2Cl2 (100 mL) and pyridine removed by extraction with 10% HCl (4×13 mL). The organic layer was dried (MgSO4) and concentrated to a yellow oil which was purified by flash chromatography (silica gel, using 5:4 petroleum ether-ether) affording 7.8 g (80%) of 5 as colorless needles: mp 91°-92° C.; TLC Rf 0.15 (4:2 ethyl ether-petroleum ether); [α25D -26° (c 1.1, CHCl3); 1H NMR (250 MHz, CDCl3) δ 7.75 (app d, J=8.4 Hz, 2 H), 7.34-7.28 (m, 7 H), 5.18-5.04 (m, 3 H, PhCH2 and H-4), 4.52-4.41 (m, 1 H, H-2), 4.20-4.02 (m, 2 H, CO2CH2CH3), 3.78-3.62 (m, 1 H, H-5), 2.48-2.37 (m, 2 H, H-3), 2.45+2.44 (s, 3 H, PhCH3, two rotamers), 1.22+1.14 (t, J=7.1 Hz, 3 H, CO2CH2CH3); 13C NMR (75.5 MHz, CDCl3) δ 170.89, 170.57, 154.20, 153.89, 145.12, 145.09, 136.11, 133.88, 129.91, 129.85, 128.38, 128.32, 128.03, 127.98, 127.86, 127.77, 127.58, 78.62, 77.74, 67.21, 67.15, 61.47, 57.53, 57.30, 52.25, 51.99, 37.07, 35.98, 21.59, 13.92, 13.85; IR (CHCl3) 2995, 1745, 1700, 1415, 1360, 1175, 1120, 1050, 1020 cm1. Anal. Calcd for C22H25NO7S: C, 59.05; H, 5.63; N, 3.13. Found: C, 59.08; H, 5.54; N, 3.11.
