Reaction Steps
To a solution of N-CBZ-trans-4-hydroxy-L-proline ethyl ester (5.6 g, 19 mmol) and anhydrous pyridine (4.6 mL, 4.5 g, 57 mmol) in CHCl3 (30 mL) was added p-toluenesulfonyl chloride (7.2 g, 38 mmol) in one portion. After stirring at room temperature for 72 h, the reaction was diluted with CH2Cl2 (70 mL) and pyridine removed by repeated extraction with 10% HCl (4×10 mL). The organic layer was dried (MgSO4) and concentrated to a golden oil which was purified by silica gel flash chromatography (gradient elution, using 1:1, 2:1 ethyl ether-petroleum ether) to yield 8.2 g (98%) of pure 2 as a colorless oil: TLC Rf 0.27 (3:3:1 ethyl ether-petroleum ether-CH2CL2); [α]24D -29° (c 1.5, CHCl3); 1H NMR (250 MHz, CDCl3 δ 7.79-7.74 (m, 2 H), 7.37-7.26 (m, 7 H), 5.18-5.00 (m, 3H, phCH2 and H-4), 4.44 (app q, J=7.5 Hz, 1 H, H-2), 4.19-3.99 (q, J=7.1 Hz, 2H, CO2CH2CH3, two rotamers), 3.76-3.60 (m, 2 H, H-5), 2.62-2.38 (m, 1 H, H-3), 2.45+2.43 (s, 3 H, PhCH3), 2.23-2.08 (m, 1 H, H-3), 1.25+1.08 (t, J=7.1 Hz, 3 H, CO2CH2CH3); 13C NMR (75.5 MHz, CDCl3) δ 171.59, 171.39, 154.12, 153.64, 145.10, 135.96, 135.81, 133.14, 133.08, 129.88, 129.86, 128.25, 128.17, 127.85, 127.60, 127.48, 78.66, 78.00, 67.14, 67.11, 61.25, 61.17, 57.39, 57.07, 52.25, 51.87, 36.99, 35.86, 21.41, 13.84, 13.69; IR (CHCl3) 1740, 1705, 1420, 1355, 1175 cm-1 ; LRMS (EI, 70 eV) m/e 447 (M+, 0.23), 374 (2), 202 (2), 158 (24), 91 (100); HRMS (EI, 40 eV) m/e 447.1337 (447.1351 calcd for C22H25NO7S).
