[CH3:1][C:2](=[N:4][OH:5])[CH3:3].C([Li])CCC.[C:11]([NH:19][C:20]1[S:21][CH2:22][C@@H:23]2[CH2:29][C@H:28]([C:30](OC)=O)[O:27][CH2:26][C@:24]2([C:34]2[CH:39]=[C:38]([Br:40])[CH:37]=[CH:36][C:35]=2[F:41])[N:25]=1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.S(=O)(=O)(O)O.[OH-].[Na+]>O1CCCC1>[Br:40][C:38]1[CH:37]=[CH:36][C:35]([F:41])=[C:34]([C@:24]23[CH2:26][O:27][C@@H:28]([C:30]4[O:5][N:4]=[C:2]([CH3:3])[CH:1]=4)[CH2:29][C@H:23]2[CH2:22][S:21][C:20]([NH:19][C:11](=[O:18])[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[N:25]3)[CH:39]=1A solution of propan-2-one oxime (0.216 g, 2.96 mmol) in tetrahydrofuran (10 mL) was cooled to 0° C. To this solution was added n-butyllithium (2.5 M in hexanes, 2.40 mL, 6.00 mmol) in a drop-wise manner. The resulting solution was allowed to warm to room temperature and left stirring at room temperature for 25 minutes. The resulting solution was cooled again to 0° C., followed by a drop-wise addition of methyl (4aR,6R,8aS)-2-(benzoylamino)-8a-(5-bromo-2-fluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxylate (C35) (1.09 g, 2.03 mmol) in tetrahydrofuran (3 mL). The reaction mixture was allowed to warm to room temperature and was left stirring for 25 minutes. The reaction mixture was cooled to 0° C. again, and sulfuric acid (0.840 mL, 15.8 mmol) was added in a drop-wise manner. The reaction mixture was allowed to warm up to room temperature and was left stirring for 16 hours at room temperature. The reaction mixture was basified to pH 12 with sodium hydroxide (5 N, ˜4 mL) and then extracted with ethyl acetate (3×100 mL). The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure to give an oily residue. Purification via silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) afforded the product as a white solid. Yield: 330 mg, 63%. LCMS m/z 532.2 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 8.12 (br s, 1H), 7.47-7.61 (m, 4H), 7.19 (dd, J=12.0, 8.9 Hz, 1H), 4.97 (br d, J=9.4 Hz, 1H), 4.31 (dd, J=11.8, 1.5 Hz, 1H), 4.00-4.14 (m, 2H), 3.00 (dd, J=13.2, 4.0 Hz, 1H), 2.83 (dd, J=13.1, 2.9 Hz, 1H), 2.10 (d, J=12.1 Hz, 1H).
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