1,4-Dioxane → HCID 71543110, compound

Participants

Reaction Steps

To a solution of (S)-4-(2-(2-((4-(N-(tert-butoxycarbonyl)methylsulfonamido)benzyl)(methyl)amino)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)ethyl)-3,5-dichloropyridine 1-oxide (0.250 g, 0.323 mmol) in DCM (15 ml), HCl 4M in dioxane (2 ml, 8.00 mmol) was added, and the solution was stirred at RT overnight. The mixture was portioned between DCM and 5% NaHCO3, and the organic layer was dried over sodium sulfate. The solvent was removed, and the crude was purified by flash chromatography on silica gel cartridge (DCM:MeOH=99:1 to 97:3) to give (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(methyl(4-(methylsulfonamido)benzyl)amino)-acetoxy)ethyl)pyridine 1-oxide, free base (0.120 g, 0.178 mmol, 55.1% yield), as a colorless amorphous solid. This product was dissolved in DCM (12 ml) and HCl 4M in dioxane (0.089 ml, 0.356 mmol) was added; the mixture was stirred at RT for 2 hours, and volatiles were removed under vacuum. The product was further dissolved in DCM and washed with 5% NaHCO3. The organic phase was dried over Na2SO4, and the crude was purified by chromatography on silica gel cartridge (DCM/EtOAc 90/10 to EtOAc 100%) followed by a further filtration through a silica gel cartridge (DCM/MeOH 99/1 to 98/2) to give 0.090 g of free base. This product was dissolved in 5 ml of DCM, and HCl 4M in dioxane (0.044 ml, 0.177 mmol) was added. The mixture was stirred at RT for 1 hour. The solvent was removed to give (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(methyl-(4-(methylsulfonamido)benzyl)amino)acetoxy)ethyl)pyridine 1-oxide hydrochloride (0.095 g, 0.134 mmol, 41.5% yield, MS/ESI+ 673.99 [MH]+)

Provenance & Evidence