Reaction Steps
Formic acid (116 mL) was added to N-((4aS,5S,7aS)-7a-(2,3-difluorophenyl)-5-((trityloxy)methyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (33.30 g, 0.051 mol, 1.0 equiv.), the mixture was stirred at r.t for 25 min. Water (17 mL) was added dropwise then the reaction was stirred for another 30 min. The resulting suspension was filtered; the filtrate was dried by azeotropic distillation under vacuum with toluene (360 mL). Methanol (110 mL) was added followed by triethylamine (22 mL, 0.15 mol, 3.0 equiv.) and the solution was stirred for 2 h. The solvent was removed under vacuum and chased with toluene (66 mL). The residual oil was dissolved in CH2Cl2 (250 ml) and washed successively with aq.HCl (1M, 100 mL), sat aq.NaHCO3 (67 mL) and 18% aq.NaCl (67 mL). The organic phase was concentrated under reduce pressure. Toluene (66 mL) and THF (67 mL) were added to the residue then the solution was filtered through celite and concentrated under reduced pressure to yield the title compound (21 g). 1H NMR (500 MHz, DMSO) ppm 8.11 (dd, J=16.4, 4.2 Hz, 2H), 7.70-7.58 (m, 1H), 7.57-7.44 (m, 3H), 7.43-7.34 (m, 1H), 7.34-7.26 (m, 1H), 4.43 (d, J=9.5 Hz, 1H), 4.25-4.16 (m, 1H), 4.10 (d, J=9.2 Hz, 1H), 3.59 (d, J=4.5 Hz, 2H), 3.30-3.21 (m, 1H), 3.20-3.08 (m, 2H); 13C NMR (125 MHz, DMSO) δ ppm 169.08, 150.95 (dd, JCF=245.8, 13.1 Hz), 148.22, 148.09 (dd, JCF=248.7, 13.2 Hz), 133.46, 129.11, 128.99, 128.62, 125.43, 124.70, 118.16 (d, JCF=16.9 Hz), 81.36, 75.29, 66.76, 62.39, 40.77, 24.25.
