Reaction Steps
The carboxylate salt 2-16 (0.084 g, 0.204 mmol) was dissolved in THF/MeOH/H2O (6:3:1, 9 mL) and the solution cooled to 0° C. LiOH.H2O (0.045 g, 1.07 mmol) dissolved in 0.4 mL H2O was added. The mixture was stirred at 0° C. for 20 hours. The solvent was removed under reduced pressure to give a white solid (Rf=0.31, CH2Cl2:MeOH 10:1). The white solid was dissolved in MeOH followed by addition of ammonium formate (0.106 g, 1.68 mmol) and Pd/C (10%, 0.049 g) under N2. The mixture was refluxed for 3 hours. The solution was then cooled, filtered through celite and syringe filter and the filtrate concentrated on a rotary evaporator to afford a white solid. The solid was dissolved in acetone/H2O (2:1, 9 mL) and cooled to 0° C., followed by the addition of Fmoc-OSu (0.067 g, 0.199 mmol) and NaHCO3 (0.16 g, 1.90 mmol). The turbid reaction mixture was stirred at 0° C. for 1 hour and was then allowed to stir at room temperature overnight. Acetone was mostly removed under reduced pressure. The aqueous residue was diluted with H2O (2 mL), diethyl ether (9 mL) added and the mixture stirred at room temperature for 1 hour. The layers were separated and the ether layer was washed three times with saturated NaHCO3. The aqueous phases were combined, acidified with 1N HCl and extracted three times with ethyl acetate (75 mL total volume). The combined organic extracts were dried over MgSO4, concentrated on a rotary evaporator, and dried under vacuum to afford a white solid. The crude product was purified by three crystallizations from n-hexane/chloroform to afford 0.05 g (53% yield) of 2-18 as white fluffy crystals: m.p. 206-208° C.; Rf=0.44, 10:1 CH2Cl2:MeOH; [α]23D=−36.0 (c 0.50, acetone); 1H NMR (300 MHz, CDCl3/CD3OD) δ 7.77 (d, J=7.5 Hz, 2H, ArH), 7.62 (d, J=6.9 Hz, 2H, ArH), 7.43-7.29 (m, 4H, ArH), 4.36-4.22 (m, 3H), 4.07-4.02 (m, 1H), 3.93-3.86 (m, 1H), 3.09-2.82 (m, 2H), 2.44-2.38 (m, 1H), 2.02-1.97 (m, 1H), 1.50-1.43 (m, 1H), 1.47 (s, 9H); 13C NMR (75 MHz, CDCl3/CD3OD) δ 173.38 (C), 155.83 (C), 154.21 (C), 143.23 (C), 140.69 (C), 127.07 (CH), 126.46 (CH), 124.42 (CH), 119.27 (CH), 80.00 (C), 66.35 (CH2), 49.73 (CH), 47.77 (CH), 46.57 (CH), 44.33 (CH2), 41.68 (CH2), 30.63 (CH2), 27.51 (CH3); MS-ESI m/z 243.1 [M−Fmoc]−, 465.1 [M−H]−, 931.2 [2M−H]−.
