3-bromo-2-chloro-6-methyl-1-oxidopyridin-1-ium

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step b—A solution of 52a (0.5 g) and 0.5 M NaOMe/MeOH (4.9 mL) was stirred at RT overnight. The reaction mixture was concentrated in vacuo and the residue loaded on a SiO2 column and eluted with 5% MeOH/DCM to afford 3-bromo-2-methoxy-6-methyl-pyridine 1-oxide (52b). The reaction mixture was concentrated in vacuo eluted with 5% MeOH/DCM

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step a—To a solution of 3-bromo-2-chloro-6-methyl-pyridine (2.0 g, 0.687 mmol) in CHCl3 was added MCPBA (3.3 g, 19.1 mmol) and the resulting solution was heated at 50° C. overnight, The resulted solution was cooled and partitioned between DCM and sat'd. aq. NaHCO3. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30 to 80% EtOAc) to afford 1.88 g (87%) of 3-bromo-2-chloro-6-methyl-pyridine 1-oxide (52a) as a white solid. The resulted solution was cooled partitioned between DCM The organic layer was dried (Na2SO4) filtered concentrated in vacuo The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30 to 80% EtOAc)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step a—To a solution of 3-bromo-2-chloro-6-methyl-pyridine (2.0 g, 0.687 mmol) in CHCl3 was added MCPBA (3.3 g, 19.1 mmol) and the resulting solution was heated at 50° C. overnight, The resulted solution was cooled and partitioned between DCM and sat'd. aq. NaHCO3. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30 to 80% EtOAc) to afford 1.88 g (87%) of 3-bromo-2-chloro-6-methyl-pyridine 1-oxide (52a) as a white solid. The resulted solution was cooled partitioned between DCM The organic layer was dried (Na2SO4) filtered concentrated in vacuo The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30 to 80% EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step b—A solution of 357a (0.5 g) and 0.5 M NaOMe/MeOH (4.9 mL) was stirred at RT overnight. The reaction mixture was concentrated in vacuo and the residue loaded on a SiO2 column and eluted with 5% MeOH/DCM to afford 3-bromo-2-methoxy-6-methyl-pyridine 1-oxide (357b). The reaction mixture was concentrated in vacuo eluted with 5% MeOH/DCM

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step a—To a solution of 3-bromo-2-chloro-6-methyl-pyridine (2.0 g, 0.687 mmol) in CHCl3 was added MCPBA (3.3 g, 19.1 mmol) and the resulting solution was heated at 50° C. overnight. The resulted solution was cooled and partitioned between DCM and sat'd. aq. NaHCO3. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30 to 80% EtOAc) to afford 1.88 g (87%) of 3-bromo-2-chloro-6-methyl-pyridine 1-oxide (357a) as a white solid. The resulted solution was cooled partitioned between DCM The organic layer was dried (Na2SO4) filtered concentrated in vacuo The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30 to 80% EtOAc)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step a—To a solution of 3-bromo-2-chloro-6-methyl-pyridine (2.0 g, 0.687 mmol) in CHCl3 was added MCPBA (3.3 g, 19.1 mmol) and the resulting solution was heated at 50° C. overnight. The resulted solution was cooled and partitioned between DCM and sat'd. aq. NaHCO3. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30 to 80% EtOAc) to afford 1.88 g (87%) of 3-bromo-2-chloro-6-methyl-pyridine 1-oxide (357a) as a white solid. The resulted solution was cooled partitioned between DCM The organic layer was dried (Na2SO4) filtered concentrated in vacuo The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30 to 80% EtOAc)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-2-chloro-6-methylpyridine (1 g, 4.84 mmol) and urea hydrogen peroxide (911 mg, 9.69 mmol) in DCM (24 mL) at 0° C. was added trifluoroacetic anhydride (1.4 mL, 9.69 mmol). After warming to 25° C. over 12 h, the solution was partitioned between H2O-DCM. The aqueous phase was washed several times with DCM and the combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (silica, 1% MeOH in DCM) yielding the title compound (1.1 g, quant.) as a white solid: LCMS (ES) m/z=223 (M+H)+. the solution was partitioned between H2O-DCM The aqueous phase was washed several times with DCM the combined organic fractions were dried over Na2SO4 concentrated purified via column chromatography (silica, 1% MeOH in DCM)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step b—A solution of 52a (0.5 g) and 0.5 M NaOMe/MeOH (4.9 mL) was stirred at RT overnight. The reaction mixture was concentrated in vacuo and the residue loaded on a SiO2 column and eluted with 5% MeOH/DCM to afford 3-bromo-2-methoxy-6-methyl-pyridine 1-oxide (52b). The reaction mixture was concentrated in vacuo eluted with 5% MeOH/DCM

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step a—To a solution of 3-bromo-2-chloro-6-methyl-pyridine (2.0 g, 0.687 mmol) in CHCl3 was added MCPBA (3.3 g, 19.1 mmol) and the resulting solution was heated at 50° C. overnight, The resulted solution was cooled and partitioned between DCM and sat'd. aq. NaHCO3. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30 to 80% EtOAc) to afford 1.88 g (87%) of 3-bromo-2-chloro-6-methyl-pyridine 1-oxide (52a) as a white solid. The resulted solution was cooled partitioned between DCM The organic layer was dried (Na2SO4) filtered concentrated in vacuo The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30 to 80% EtOAc)