Reaction Steps
A suspension of ((2S,3R,4S)-4-amino-4-(2,3-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanol (−)dibenzoyl-L-tartaric acid (44.21 g, 0.051 mol, 1.0 equiv.) in EtOAc (133 mL) was cooled down to 1.7° C. Aq. NaOH (1.0 M, 121 mL, 0.12 mol, 2.4 equiv.) was added while maintaining temperature below 5° C. The reaction was stirred for 5 min then benzyl isothiocyanate (9.43 g, 0.058 mol, 1.12 equiv.) was added over 5 min. After 1.5 h, EtOAc (133 mL) was added. The organic phase was isolated and successively washed with saturated aq. NaHCO3 (130 mL) and 18% aq.NaCl (44 mL). The combined aqueous phases were extracted with EtOAc (66 mL) and CH2Cl2 (30 mL). All the organic phase were combined, filtered and concentrated under reduced pressure. The title compound (34.2 g) was isolated as a foam after chasing the residual solvent with CH2Cl2 (88 mL). 1H NMR (500 MHz, DMSO) δ ppm 11.97 (br s, 1H), 11.20 (br s, 1H), 7.94 (d, J=7.4 Hz, 2H), 7.63 (t, J=7.4 Hz, 1H), 7.51 (t, J=7.8 Hz, 2H), 7.38-7.21 (m, 17H), 7.13 (dd, J=13.4, 7.9 Hz, 1H), 5.13 (t, J=4.4 Hz, 1H), 5.07 (d, J=9.7 Hz, 1H), 4.47 (d, J=9.8 Hz, 1H), 4.24-4.16 (m, 1H), 3.68 (t, J=4.6 Hz, 2H), 3.19 (dd, J=10.1, 2.9 Hz, 1H), 3.01 (dd, J=10.1, 4.8 Hz, 1H), 2.63-2.52 (m, 1H); 13C NMR (125 MHz, DMSO) δ ppm 180.06, 168.14, 150.75 (dd, JCF=244.6, 13.2 Hz), 147.93 (dd, JCF=247.5, 13.5 Hz), 144.15, 133.46, 132.55, 131.90 (d, JCF=6.4 Hz), 129.04, 128.86, 128.67, 128.28, 127.43, 124.41, 124.25, 116.12 (d, JCF=17.0 Hz), 86.27, 79.75, 75.03, 68.04, 64.63, 58.16, 53.35.
