Reaction SMILES: [OH:1][CH:2](CO)[CH2:3][C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:5]=1[N:14]1[CH2:19][CH2:18][O:17][C:16]2[CH:20]=[C:21]([S:24]([N:27]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)[C:28]3[S:29][CH:30]=[CH:31][N:32]=3)(=[O:26])=[O:25])[CH:22]=[CH:23][C:15]1=2.O.I([O-])(=O)(=O)=O.[Na+]>C1COCC1>[CH3:41][O:40][C:37]1[CH:36]=[CH:35][C:34]([CH2:33][N:27]([C:28]2[S:29][CH:30]=[CH:31][N:32]=2)[S:24]([C:21]2[CH:22]=[CH:23][C:15]3[N:14]([C:5]4[CH:6]=[CH:7][C:8]([C:10]([F:11])([F:12])[F:13])=[CH:9][C:4]=4[CH2:3][CH:2]=[O:1])[CH2:19][CH2:18][O:17][C:16]=3[CH:20]=2)(=[O:26])=[O:25])=[CH:39][CH:38]=1
Reactant: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(c2)OCCN3c2ccc(C(F)(F)F)cc2CC(O)CO)cc1
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(c2)OCCN3c2ccc(C(F)(F)F)cc2CC=O)cc1
Temperature: 25 °C
Reaction time: 0.83 h

Procedure:
To a solution of 4-(2-(2,3-dihydroxypropyl)-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (from EXAMPLE 207, intermediate from Step 2; 0.100 g, 0.157 mmol) in THF (0.605 ml)/water (0.605 ml) was added sodium periodate (0.050 g, 0.236 mmol). The reaction mixture was stirred at RT for 50 minutes (reaction turned from white slurry to yellow upon addition of sodium periodate). Upon completion, the reaction was filtered and washed well with THF. The filtrate was concentrated in vacuo to yield crude N-(4-methoxybenzyl)-4-(2-(2-oxoethyl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide, which was dissolved in methanol (1.573 ml, 0.157 mmol) and to the solution was added sodium borohydride (0.012 g, 0.315 mmol) at 0° C. (turned from yellow to clear solution upon addition), and the reaction was stirred in the ice-bath for 20 minutes until completion. The reaction was quenched with sat. ammonium chloride solution (aq) and washed with DCM (×2). After drying via phase separator (Radley's Discovery Technology), the organics were concentrated in vacuo to yield an orange oil. The oil was taken up in DCM, and TFA was added (color change from orange solution to light pink). The reaction was stirred for 6 h, at which time product was observed (along with TFA adduct of the alcohol). Upon concentrating in vacuo, the material fully converted to the TFA adduct. The material was dissolved in methanol, and a few drops of sodium methoxide solution (in methanol) were added. After 1 h, the reaction was neutralized with ammonium chloride solution (aq) and was extracted with DCM (×2) and then the organics were dried via phase separator, and concentrated in vacuo. Upon attempting to dissolve the crude material in DCM for silica gel chromatography, the material would not go into solution. Instead, methanol was added (solubilizing it) and then it was purified via 2-g SCX column (product eluted with methanol wash) to yield product (with some impurities) as a white solid. The material was lastly purified via silica gel chromatography, eluting with 0-100% ethyl acetate in heptane to yield 4-(2-(2-hydroxyethyl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.69-2.76 (m, 2 H) 3.53-3.62 (m, 3 H) 3.72-3.80 (m, 1 H) 4.32-4.42 (m, 2 H) 4.68 (t, J=5.28 Hz, 1 H) 6.08 (d, J=8.51 Hz, 1 H) 6.78 (d, J=4.60 Hz, 1 H) 7.09 (dd, J=8.51, 2.15 Hz, 1 H) 7.14 (d, J=2.05 Hz, 1 H) 7.21 (d, J=4.50 Hz, 1 H) 7.52 (d, J=8.51 Hz, 1 H) 7.69 (dd, J=8.46, 2.01 Hz, 1 H) 7.81 (d, J=1.76 Hz, 1 H) 12.54 (br. s., 1 H). m/z (ESI) 486.0 (M+H)+.