To iron (8.03 g, 0.144 mol, 6.0 equiv.) was added ethanol (66.56 mL), followed by conc. HCl (62%, 1.2 mL, 0.014 mol, 0.60 equiv.). The mixture was heated to 65° C. for 2 h, and then sat NH4Cl (33%, 33.3 mL) was added and the reaction temperature was maintained at 55° C. A solution of (4aS,5S,7aS)-7a-(2,3-difluoro-5-nitrophenyl)-5-(fluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine (8.32 g, 0.024 mol, 1.0 equiv.) and conc. HCl (1.93 mL, 0.024 mol, 1.0 equiv.) in ethanol (41.6 mL) was added to the iron suspension. The reaction was stirred for 30 min at 55° C., then ethanol (50 mL) was added and the suspension was allowed to cool down to 20° C., filtered through celite (8.3 g) and rinsed with ethanol (125 mL). The filtrate was concentrated under reduced pressure then water (66 mL) was added, followed by 3.0 M aq.NaOH (24 mL, 0.0179 mol, 3.0 equiv.). The resulting mixture was extracted with CH2Cl2 (2×83 mL). The organics phases were combined and filtered over celite and concentrated under reduce pressure to give the title compound (7.60 g). 1H NMR (500 MHz, DMSO) δ ppm 6.42-6.35 (m, 2H), 6.02 (brs, 2H), 4.66-4.41 (m, 2H), 4.37-4.25 (m, 1H), 4.21 (d, J=8.0 Hz, 1H), 3.69 (dd, J=7.8, 2.2 Hz, 1H), 2.97 (qd, J=13.5, 3.4 Hz, 3H), 2.74-2.64 (m, 1H); 13C NMR (125 MHz, DMSO) δ ppm 151.08 (dd, JCF=240.1, 14.8 Hz), 148.88, 145.40 (d, JCF=10.7 Hz), 139.33 (dd, JCF=233.5, 13.8 Hz), 132.53 (d, JCF=8.1 Hz), 109.90, 100.70 (d, JCF=20.0 Hz), 83.99 (d, JCF=169.9 Hz), 78.79 (d, JCF=18.3 Hz), 77.99 (d, JCF=5.5 Hz), 66.22, 36.24, 23.14.
