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b) (3,5-Difluoro-4-nitro-phenyl)-methanol To a solution of 3,5-difluoro-4-nitro-benzoic acid methyl ester (10.95 g, 50 mmol) in THF (250 mL) is added at 0-5 C. under argon a 1M DIBAL solution in hexane (165 mL, 165 mmol) within 1.5 h. The reaction mixture is stirred for 2.5 h at 0-5 C. before it is added to 200 mL cold 1M aqueous potassium tartrate solution under ice-cooling. After stirring the reaction mixture for 0.5 h at 25 C., the aqueous phase is extracted with EtOAc. Combined organic extracts are washed with brine, dried over MgSO4, filtered and evaporated to provide the title compound as a yellow solid: TLC (hexane-EtOAc 1.1) Rf=0.35; HPLC RtA=1.31 min; 1H-NMR (400 MHz, CDCl3): delta 7.12 (d, 2H), 4.77 (s, 2H).
With phosphorus tribromide; In diethyl ether; at 0 - 25℃; for 24h;
c) 5-Bromomethyl-1,3-difluoro-2-nitro-benzene To a solution of PBr3 (7.04 mL, 73 mmol) in Et2O (200 mL) is added under Argon at 0 C. a solution of <strong>[1123172-89-3](3,5-difluoro-4-nitro-phenyl)-methanol</strong> (9.3 g, 48.7 mmol) in Et2O (200 mL). The reaction mixture is allowed to warm to 25 C. and stirred for 24 h at 25 C. After the addition of MeOH (5 mL) at 0 C., the reaction mixture is poured onto cold NaHCO3 solution and the product is extracted with EtOAc. Combined organic extracts are washed with NaHCO3-solution and brine, dried over MgSO4, filtered and concentrated to provide the title compound after filtration through a plug of silicagel with hexane-EtOAc 3:1 as a yellow solid: TLC (hexane-EtOAc 3:1) Rf=0.40; HPLC RtA=2.01 min; 1H-NMR (400 MHz, CDCl3): delta 7.14 (d, 2H), 4.40 (s, 2H).
(3S,4S,5R)-3-(4-amino-3-(2,2-difluoroethoxy)-5-fluorobenzyl)-5-((3-(tert-butyl)benzyl)amino)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide dihydrochloride[ No CAS ]
(3S,4S,5R)-3-(4-amino-3-fluoro-5-(3,3,3-trifluoropropoxy)benzyl)-5-((3-(tert-butyl)benzyl)-amino)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide dihydrochloride[ No CAS ]
(3S,4S,5R)-3-(4-amino-3-fluoro-5-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)benzyl)-5-((3-(tertbutyl)benzyl)amino)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide dihydrochloride[ No CAS ]
(3S,4S,5R)-3-(4-amino-3-fluoro-5-(2-methoxyethoxy)benzyl)-5-((3-(tert-butyl)benzyl)amino)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide dihydrochloride[ No CAS ]
(3aR,7S,7aS)-7-(4-amino-3-fluoro-5-isopropoxybenzyl)-3-(3-(tert-butyl)benzyl)hexahydro-2H2Hthiopyrano[3,4-d]oxazol-2-one 5,5-dioxide dihydrochloride[ No CAS ]
(3S,4S,5R)-3-(4-amino-3-fluoro-5-(((R)-1,1,1-trifluoropropan-2-yl)oxy)benzyl)-5-((3-(tertbutyl)amino)-4-hydroxytetrahydro)-2H-thiopyran 1,1-dioxide dihydrochloride[ No CAS ]
(3S,4S,5R)-3-(4-amino-3-fluoro-5-(((R)-1,1,1-trifluoro-3-methoxypropan-2-yl)oxy)benzyl)-5-((3-(tert-butyl)benzyl)amino)-4-hydroxy-hydroxytetrahydro-2H-thiopyran 1,1-dioxide dihydrochloride[ No CAS ]
(3S,4S,5R)-3-(4-amino-3-fluoro-5-(((R)-1,1,1-trifluoro-3-(2-methoxyethoxy)propan-2-yl)oxy)benzyl)-5-((3-(tert-butyl)benzyl)-amino)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide dihydrochloride[ No CAS ]
(3S,4S,5R)-3-(4-amino-3-fluoro-5-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)benzyl)-4-hydroxy-5-((3-(1-hydroxy-2-methylpropan-2-yl)benzyl)amino)tetrahydro-2H-thiopyran 1,1-dioxide dihydrochloride[ No CAS ]
(3S,4S,5R)-3-(4-amino-3-fluoro-5-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)benzyl)-5-(((3,3-dimethyl1,3-dihydroisobenzofuran-5-yl)methyl)amino)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide dihydrochloride[ No CAS ]
(3S,4S,5R)-3-(4-amino-3-fluoro-5-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)benzyl)-5-((((1R,2S)-2-(tert-butoxy)cyclopropyl)methyl)amino)-4-hydroxytetrahydro-2H-thiopyran-1,1-dioxide hydrochloride[ No CAS ]
2-(tert-butoxy)-N-((3R,4S,5S)-5-(3-fluoro-5-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)-4-nitrobenzyl)-4-hydroxy)-1,1-dioxidotetrahydro-2H-thiothiopyran-cyclopropanecarboxamide[ No CAS ]
N-((3R,4S,5S)-5-(4-amino-3-fluoro-5-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)benzyl)-4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)-((1RS,2SR)-2-(tert-butoxy)cyclopropanecarboxamide)[ No CAS ]