Reaction SMILES: F[C:2]([F:15])(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[F:16][C:17]1C(F)=[CH:21][CH:20]=[CH:19][C:18]=1[C@@:24]1([NH:52][C:53]([NH:55][C:56](=[O:63])[C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)=[S:54])[C@H:28]([CH2:29]O)[C@@H:27]([CH2:31][O:32][C:33]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:26][CH2:25]1.C(=O)(O)[O-].[Na+].CCOC(C)=O>N1C=CC=CC=1>[F:16][C:17]1[C:2]([F:15])=[CH:21][CH:20]=[CH:19][C:18]=1[C@:24]12[CH2:25][O:26][C@H:27]([CH2:31][O:32][C:33]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)[C@H:28]1[CH2:29][S:54][C:53]([NH:55][C:56](=[O:63])[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)=[N:52]2
Reactant: O=C(NC(=S)N[C@@]1(c2cccc(F)c2F)CO[C@H](COC(c2ccccc2)(c2ccccc2)c2ccccc2)[C@H]1CO)c1ccccc1
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: O=C(NC1=N[C@@]2(c3cccc(F)c3F)CO[C@H](COC(c3ccccc3)(c3ccccc3)c3ccccc3)[C@H]2CS1)c1ccccc1
Reaction time: 0.67 h

Procedure:
Trifluoromethanesulfonic anhydride (3 ml) was added to a solution of N-(((3S,4R,5S)-3-(2,3-difluorophenyl)-4-(hydroxymethyl)-5-((trityloxy)methyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide, obtained in Preparation Example 4-(24), (9.47 g) in pyridine (35 ml) at 0° C. under nitrogen atmosphere. After stirring for 1 h and 40 mins at the same temperature, the mixture was poured into saturated aqueous sodium bicarbonate and EtOAc was added. The organic layer was separated and washed with water and brine, then dried over MgSO4. The solid was removed by filtration, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (gradient from 30% to 70% EtOAc in heptane). The obtained crude compound was purified again by silica gel column chromatography (gradient from 10% to 35% EtOAc in heptane) to afford the titled compound (8.34 g) as a pale yellow solid. 1H-NMR (400 MHz, CDCl3) δ (ppm): 2.68 (dd, J=13.6, 3.2 Hz, 1H), 3.11-3.14 (m, 1H), 3.32-3.36 (m, 2H), 3.42-3.46 (m, 1H), 4.04 (d, J=9.2 Hz, 1H), 4.54-4.60 (m, 2H), 7.13-7.33 (m, 11H), 7.37-7.53 (m, 10H), 8.11-8.13 (m, 2H) 4-(26) N-((4aS,5S,7aS)-7a-(2,3-Difluorophenyl)-5-(hydroxymethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (also called 1-(6) and 4-(12)) Formic acid (35 ml) was added to a solution of 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, obtained in Preparation Example 4-(25), (8.79 g) in ether (35 ml) at RT. After stirring for 15.25 h at RT, the mixture was concentrated in vacuo to approximately half of the original volume. Formic acid (15 ml) was added to the residue at RT. After stirring for 4 h at RT, the mixture was concentrated in vacuo. Methanol (450 ml) and TEA (9 ml) were added to the residue and the mixture stirred for 1 h at reflux. Further TEA (9 ml) was added and the mixture stirred for 3 h at reflux. The resultant mixture was concentrated in vacuo, and saturated ammonium chloride aqueous solution was added. The mixture was extracted with EtOAc and washed with saturated ammonium chloride solution and brine. The obtained organic layer was dried over MgSO4, and the solid was removed by filtration. The filtrate was concentrated in vacuo and purified by silica gel column chromatography (gradient from 50% to 100% EtOAc in heptane) to afford the targeted compound (5.5 g) as a pale yellow solid. 1H-NMR (400 MHz, CDCl3) δ (ppm): 2.80-2.84 (m, 1H), 3.20-3.24 (m, 1H), 3.35-3.38 (m, 1H), 3.73-3.77 (m, 1H), 3.94-3.97 (m, 1H), 4.05-4.08 (m, 1H), 4.51-4.56 (m, 2H), 7.12-7.24 (m, 3H), 7.43-7.47 (m, 2H), 7.51-7.55 (m, 1H), 8.10-8.12 (m, 2H) 4-(27) N-((4aS,5S,7aS)-7a-(2,3-Difluorophenyl)-5-(fluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (also called 4-(13) TEA (14.9 ml), triethylamine trihydrofluoride complex (5.83 ml), and perfluorobutanesulfonyl fluoride (6.17 ml) were added sequentially to a solution of N-((4aS,5S,7aS)-7a-(2,3-Difluorophenyl)-5-(hydroxymethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide, obtained in Preparation Example 4-(26), (3.83 g) in THF (60 ml) at 0° C. After stirring for 2 h at the same temperature, the mixture was allowed to warm to RT then stirred for 1 h and 20 mins again at RT. Further triethylamine trihydrofluoride complex (4.37 ml) was added then the mixture was stirred for 1 h and 10 mins again at RT. Further TEA (7.49 ml) and perfluorobutanesulfonyl fluoride (3.09 ml) were added and the mixture stirred at RT for 1 h. The resultant mixture was poured into saturated aqueous sodium bicarbonate solution and extracted with EtOAc. The organic layer was dried over MgSO4, and the solid was removed by filtration. The filtrate was concentrated in vacuo, and purified by silica gel column chromatography (gradient from 30% to 100% EtOAc in heptane) to afford targeted compound (2.11 g) as a white solid. 1H-NMR (400 MHz, CDCl3) 6 (ppm): 2.83 (dd, J=13.6, 3.6 Hz, 1H), 3.24 (d, J=13.6 Hz, 1H), 3.36 (bs, 1H), 4.03 (d, J=8.8 Hz, 1H), 4.45-4.75 (m, 4H), 7.12-7.24 (m, 3H), 7.46 (t, J=7.6 Hz, 2H), 7.54 (t, J=7.2 Hz, 1H), 8.08 (d, J=4.8 Hz, 2H)