4-bromo-3,5-dimethyl-1-oxidopyridin-1-ium

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a microwave tube was added 4-bromo-3,5-dimethylpyridine 1-oxide (2.00 g, 9.90 mmol), triphenylphosphine (3.12 g, 11.9 mmol) and toluene (10 mL). The tube was sealed and heated at 180° C. overnight. The reaction solution was diluted with ethyl acetate, and filtered. The filtrate was concentrated and purified by flash chromatography (10% to 40% ethyl acetate in hexanes) to afford the desired product as a yellow oil (700 mg, 38%). 1H NMR (400 MHz, CDCl3): δ 8.22 (s, 2H), 2.38 (s, 6H); LCMS calculated for C2H9BrN(M+H)+: m/z=186.0. The tube was sealed filtered The filtrate was concentrated purified by flash chromatography (10% to 40% ethyl acetate in hexanes)

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a microwave tube was added 4-bromo-3,5-dimethylpyridine 1-oxide (2.00 g, 9.90 mmol), triphenylphosphine (3.12 g, 11.9 mmol) and toluene (10 mL). The tube was sealed and heated at 180° C. overnight. The reaction solution was diluted with ethyl acetate, and filtered. The filtrate was concentrated and purified by flash chromatography (10% to 40% ethyl acetate in hexanes) to afford the desired product as a yellow oil (700 mg, 38%). 1H NMR (400 MHz, CDCl3): δ 8.22 (s, 2H), 2.38 (s, 6H); LCMS calculated for C2H9BrN(M+H)+: m/z=186.0. The tube was sealed filtered The filtrate was concentrated purified by flash chromatography (10% to 40% ethyl acetate in hexanes)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3,5-dimethylpyridine 1-oxide (6.1 g, 50 mmol) in acetic acid (30 mL) was added thallium(III) triacetate (5.0 g, 13 mmol) and bromine (2.6 mL, 50 mmol). The resulting solution was heated at 60° C. overnight. The reaction was concentrated in vacuo, diluted with water and ethyl acetate. The organic layer was concentrated and residue was purified by silica gel chromatography to afford the desired product (5.40 g, 54%). 1H NMR (400 MHz, CDCl3): δ 7.96 (s, 2H), 2.38 (s, 6H). The reaction was concentrated in vacuo diluted with water and ethyl acetate The organic layer was concentrated residue was purified by silica gel chromatography

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flame-dried sealable Schlenk tube was charged with 4-bromo-3,5-dimethyl-pyridine 1-oxide (1; 10.1 g, 50.0 mmol), 2 (18.0 g, 100 mmol), Pd2(dba)3 (0.915 g, 1.00 mmol), dicyclohexyl-(2-phenanthren-9-yl-phenyl)-phosphane (1.8 g, 4.0 mmol), and K3PO4 (31.9 g, 150 mmol). The Schlenk tube was next evacuated and backfilled with N2. Then, degassed dry toluene (100 mL) was added via syringe under N2. The Schlenk tube was sealed, and the mixture was stirred at 120° C. for 48 h. The reaction mixture was subsequently cooled to room temperature, diluted with methylene chloride (500 mL), filtered, and concentrated in vacuo. The resulting dark brown oil was allowed to stand at room temperature until the colorless crystalline product separated from the liquid. The solid was then collected by filtration and identified as the pure title compound (6.55 g). The filtrate was purified by flash chromatography eluting with 95:5 CHCl3: methanol to afford an additional 0.23 g of the title compound. The combined yield was 6.78 g (53%): mp 194-195° C.; 1H NMR (400 MHz, CD2Cl2): δ 7.990 (s, 2H), 6.705 (s, 2H), 3.798 (s, 3H), 1.892 (s, 6H), 1.842 (s, 6H); 13C NMR (125 MHz, CD2Cl2): δ 159.771, 139.578, 137.663, 137.187, 135.775, 128.289, 113.709, 55.605, 20.198, 17.087; MS (ESI): m/z 258.4 [(M+H)+, 100]; Anal. Calcd. For C16H19NO2: C, 74.68; H, 7.44; N, 5.44. Found: C, 74.54; H, 7.40; N, 5.51. The Schlenk tube was next evacuated Then, degassed dry toluene (100 mL) was added via syringe under N2 The Schlenk tube was sealed The reaction mixture was subsequently cooled to room temperature diluted with methylene chloride (500 mL) filtered concentrated in vacuo to stand at room temperature until the colorless crystalline product separated from the liquid The solid was then collected by filtration The filtrate was purified by flash chromatography eluting with 95:5 CHCl3

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flame-dried sealable Schlenk tube was charged with 4-bromo-3,5-dimethyl-pyridine 1-oxide (1; 10.1 g, 50.0 mmol), 2 (18.0 g, 100 mmol), Pd2(dba)3 (0.915 g, 1.00 mmol), dicyclohexyl-(2-phenanthren-9-yl-phenyl)-phosphane (1.8 g, 4.0 mmol), and K3PO4 (31.9 g, 150 mmol). The Schlenk tube was next evacuated and backfilled with N2. Then, degassed dry toluene (100 mL) was added via syringe under N2. The Schlenk tube was sealed, and the mixture was stirred at 120° C. for 48 h. The reaction mixture was subsequently cooled to room temperature, diluted with methylene chloride (500 mL), filtered, and concentrated in vacuo. The resulting dark brown oil was allowed to stand at room temperature until the colorless crystalline product separated from the liquid. The solid was then collected by filtration and identified as the pure title compound (6.55 g). The filtrate was purified by flash chromatography eluting with 95:5 CHCl3: methanol to afford an additional 0.23 g of the title compound. The combined yield was 6.78 g (53%): mp 194-195° C.; 1H NMR (400 MHz, CD2Cl2): δ 7.990 (s, 2H), 6.705 (s, 2H), 3.798 (s, 3H), 1.892 (s, 6H), 1.842 (s, 6H); 13C NMR (125 MHz, CD2Cl2): δ 159.771, 139.578, 137.663, 137.187, 135.775, 128.289, 113.709, 55.605, 20.198, 17.087; MS (ESI): m/z 258.4 [(M+H)+,100]; Anal. Calcd. For C16H19NO2: C, 74.68; H, 7.44; N, 5.44. Found: C, 74.54; H, 7.40; N, 5.51. The Schlenk tube was next evacuated Then, degassed dry toluene (100 mL) was added via syringe under N2 The Schlenk tube was sealed The reaction mixture was subsequently cooled to room temperature diluted with methylene chloride (500 mL) filtered concentrated in vacuo to stand at room temperature until the colorless crystalline product separated from the liquid The solid was then collected by filtration The filtrate was purified by flash chromatography eluting with 95:5 CHCl3

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a microwave tube was added 4-bromo-3,5-dimethylpyridine 1-oxide (2.00 g, 9.90 mmol), triphenylphosphine (3.12 g, 11.9 mmol) and toluene (10 mL). The tube was sealed and heated at 180° C. overnight. The reaction solution was diluted with ethyl acetate, and filtered. The filtrate was concentrated and purified by flash chromatography (10% to 40% ethyl acetate in hexanes) to afford the desired product as a yellow oil (700 mg, 38%). 1H NMR (400 MHz, CDCl3): δ 8.22 (s, 2 H), 2.38 (s, 6 H); LCMS calculated for C7H9BrN(M+H)+: m/z=186.0. The tube was sealed filtered The filtrate was concentrated purified by flash chromatography (10% to 40% ethyl acetate in hexanes)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3,5-dimethylpyridine 1-oxide (6.1 g, 50 mmol) in acetic acid (30 mL) was added thallium(III) triacetate (5.0 g, 13 mmol) and bromine (2.6 mL, 50 mmol). The resulting solution was heated at 60° C. overnight. The reaction was concentrated in vacuo, diluted with water and ethyl acetate. The organic layer was concentrated and residue was purified by silica gel chromatography to afford the desired product (5.40 g, 54%). 1H NMR (400 MHz, CDCl3): δ 7.96 (s, 2 H), 2.38 (s, 6 H). The reaction was concentrated in vacuo diluted with water and ethyl acetate The organic layer was concentrated residue was purified by silica gel chromatography

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flame-dried sealable Schlenk tube was charged with 4-bromo-3,5-dimethyl-pyridine 1-oxide (1; 10.1 g, 50.0 mmol), 2 (18.0 g, 100 mmol), Pd2(dba)3 (0.915 g, 1.00 mmol), dicyclohexyl-(2-phenanthren-9-yl-phenyl)-phosphane (1.8 g, 4.0 mmol), and K3PO4 (31.9 g, 150 mmol). The Schlenk tube was next evacuated and backfilled with N2. Then, degassed dry toluene (100 mL) was added via syringe under N2. The Schlenk tube was sealed, and the mixture was stirred at 120° C. for 48 h. The reaction mixture was subsequently cooled to room temperature, diluted with methylene chloride (500 mL), filtered, and concentrated in vacuo. The resulting dark brown oil was allowed to stand at room temperature until the colorless crystalline product separated from the liquid. The solid was then collected by filtration and identified as the pure title compound (6.55 g). The filtrate was purified by flash chromatography eluting with 95:5 CHCl3: methanol to afford an additional 0.23 g of the title compound. The combined yield was 6.78 g (53%): mp 194-195° C.; 1H NMR (400 MHz, CD2Cl2): δ 7.990 (s, 2H), 6.705 (s, 2H), 3.798 (s, 3H), 1.892 (s, 6H), 1.842 (s, 6H); 13C NMR (125 MHz, CD2Cl2): δ 159.771, 139.578, 137.663, 137.187, 135.775, 128.289, 113.709, 55.605, 20.198, 17.087; MS (ESI): m/z 258.4 [(M+H)+, 100]; Anal. Calcd. For C16H19NO2: C, 74.68; H, 7.44; N, 5.44. Found: C, 74.54; H, 7.40; N, 5.51. The Schlenk tube was next evacuated Then, degassed dry toluene (100 mL) was added via syringe under N2 The Schlenk tube was sealed The reaction mixture was subsequently cooled to room temperature diluted with methylene chloride (500 mL) filtered concentrated in vacuo to stand at room temperature until the colorless crystalline product separated from the liquid The solid was then collected by filtration The filtrate was purified by flash chromatography eluting with 95:5 CHCl3

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a microwave tube was added 4-bromo-3,5-dimethylpyridine 1-oxide (2.00 g, 9.90 mmol), triphenylphosphine (3.12 g, 11.9 mmol) and toluene (10 mL). The tube was sealed and heated at 180° C. overnight. The reaction solution was diluted with ethyl acetate, and filtered. The filtrate was concentrated and purified by flash chromatography (10% to 40% ethyl acetate in hexanes) to afford the desired product as a yellow oil (700 mg, 38%). 1H NMR (400 MHz, CDCl3): δ 8.22 (s, 2H), 2.38 (s, 6H); LCMS calculated for C2H9BrN(M+H)+: m/z=186.0. The tube was sealed filtered The filtrate was concentrated purified by flash chromatography (10% to 40% ethyl acetate in hexanes)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3,5-dimethylpyridine 1-oxide (6.1 g, 50 mmol) in acetic acid (30 mL) was added thallium(III) triacetate (5.0 g, 13 mmol) and bromine (2.6 mL, 50 mmol). The resulting solution was heated at 60° C. overnight. The reaction was concentrated in vacuo, diluted with water and ethyl acetate. The organic layer was concentrated and residue was purified by silica gel chromatography to afford the desired product (5.40 g, 54%). 1H NMR (400 MHz, CDCl3): δ 7.96 (s, 2H), 2.38 (s, 6H). The reaction was concentrated in vacuo diluted with water and ethyl acetate The organic layer was concentrated residue was purified by silica gel chromatography