Reaction Steps
A catalytic amount of concentrated H2SO4 (4.5 mL) was added to a solution of Alloc-hydroxyproline (2) (43 g, 200 mmol) in MeOH (300 mL) at 10° C. (ice) and the reaction mixture was then heated at reflux for 2 h. After cooling to room temperature the reaction mixture was treated with TEA (43 mL) and the MeOH evaporated in vacuo. The residue was dissolved in EtOAc (300 mL), washed with brine (200 mL), dried (MgSO4), filtered and concentrated in vacuo to give a viscous oil. Purification by flash chromatography (40% EtOAc/Petroleum Ether) removed the high Rf impurity to provide the pure ester 3 as a transparent yellow oil (19.6 g, 43%): [α]23D=−79.0° (c=0.35, CHCl3); 1H NMR (270 MHz, CDCl3) (Rotamers) δ 5.98-5.78 (m, 1H, NCO2CH2CH═CH2), 5.35-5.16 (m, 2H, NCO2CH2CH═CH2), 4.65-4.45 (m, 4H, NCO2CH2CH═CH2, NCH2CHOHCH2 and NCHCO2CH3), 3.75 and 3.72 (s×2, 3H, OCH3), 3.70-3.54 (m, 2H, NCH2CHOHCH2), 3.13 and 3.01 (br s×2, 1H, OH), 2.39-2.03 (m, 2H, NCH2CHOHCH2); 13C NMR (67.8 MHz, CDCl3) (Rotamers) δ 173.4 and 173.2 (CO2CH3), 155.0 and 154.6 (NC═O), 132.6 and 132.4 (NCO2CH2CH═CH2), 117.6 and 117.3 (NCO2CH2CH═CH2), 70.0 and 69.2 (NCH2CHOH), 66.2 (NCO2CH2CH═CH2), 57.9 and 57.7 (NCHCO2CH3), 55.2 and 54.6 (NCH2CHOH), 52.4 (OCH3), 39.1 and 38.4 (NCH2CHOHCH2); MS (EI), m/z (relative intensity) 229 (M+, 7), 170 (M-CO2Me, 100), 144 (M-CO2C3H5, 12), 126 (26), 108 (20), 68 (7), 56 (8); IR (Neat) 3438 (br, OH), 2954, 1750 and 1694 (br, C═O), 1435, 1413, 1345, 1278, 1206, 1130, 1086, 994, 771 cm−1; exact mass calcd for C10H15NO5 m/e 229.0950, obsd m/e 229.0940.
