2-chloro-5-fluoro-1-oxidopyridin-1-ium

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-5-fluoropyridine-N-oxide (10, 3.5 g, 23.7 mmol) was gradually added to 46 mL of concentrated sulfuric acid, followed by 10 g of potassium nitrate with stirring. The reaction mixture was heated at 120° C. for 2 h, cooled and poured onto 160 g of crushed ice. The solution was neutralized by dropwise addition of 28% ammonium hydroxide with stirring, while the temperature was maintained below 15° C. with an ice bath. The light yellow crystals which precipitated were collected by filtration, washed with ice water, and dried to yield 2.7 g (59%) of product. A small sample was purified by silica gel column chromatography (CH2Cl2/EtOAc, 4:1, v/v, Rf 0.71): mp 131-132° C.; 1H NMR (DMSO-d6) δ8.70 (m, 1 H, 3-H), 9.12 (m, 1 H, 6-H). Analysis calculated for C5H2ClFN2O3: C, 31.19; H, 1.05; N, 14.55. Found: C, 31.36; H, 1.16; N, 14.75. cooled with stirring, while the temperature was maintained below 15° C. with an ice bath The light yellow crystals which precipitated were collected by filtration washed with ice water dried

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

実験手順: 2-Chloro-5-fluoropyridine (9), a highly volatile substance, was synthesized from thermolysis of 2-chloro-5-pyridinediazonium tetrafluoroborate (8). Hand, E. S.; Baker, D. C. Synthesis 1989, 905-908. The isolation of 9 by the literature procedure was very complicated, in that it included repeated extractions, repeated distillations, treatment with sulfuric acid and sodium hydroxide, and steam distillation. In our hands, the reported yield of 70% was difficult to obtain after these operations. To improve upon these complicated procedures, following the thermolysis of compound 8, the reaction mixture was directly treated with 50% hydrogen peroxide and trifluoroacetic acid to give 2-chloro-5-fluoropyridine-N-oxide (10), which was easily isolated, with a total yield of 73%. Nitration of 10, followed by catalytic hydrogenation of the resulting 2-chloro-5-fluoro-4-nitropyridine-1-oxide (11) removed the N-oxide function, as well as reduced the nitro group to give the desired 4-amino-2-chloro-5-fluoropyridine (12). N-Oxidation of commercially available 2,5-dichloropyridine (13), followed by nitration and reduction yielded 4-amino-2,5-dichloropyridine (16). was easily isolated, with a total yield of 73% removed the N-oxide function

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

実験手順: 2-Chloro-5-fluoropyridine (9), a highly volatile substance, was synthesized from thermolysis of 2-chloro-5-pyridinediazonium tetrafluoroborate (8). Hand, E. S.; Baker, D. C. Synthesis 1989, 905-908. The isolation of 9 by the literature procedure was very complicated, in that it included repeated extractions, repeated distillations, treatment with sulfuric acid and sodium hydroxide, and steam distillation. In our hands, the reported yield of 70% was difficult to obtain after these operations. To improve upon these complicated procedures, following the thermolysis of compound 8, the reaction mixture was directly treated with 50% hydrogen peroxide and trifluoroacetic acid to give 2-chloro-5-fluoropyridine-N-oxide (10), which was easily isolated, with a total yield of 73%. Nitration of 10, followed by catalytic hydrogenation of the resulting 2-chloro-5-fluoro-4-nitropyridine-1-oxide (11) removed the N-oxide function, as well as reduced the nitro group to give the desired 4-amino-2-chloro-5-fluoropyridine (12). N-Oxidation of commercially available 2,5-dichloropyridine (13), followed by nitration and reduction yielded 4-amino-2,5-dichloropyridine (16). Synthesis 1989, 905-908 extractions with sulfuric acid and sodium hydroxide, and steam distillation to obtain after these operations

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

実験手順: 2-Chloro-5-fluoropyridine (9), a highly volatile substance, was synthesized from thermolysis of 2-chloro-5-pyridinediazonium tetrafluoroborate (8). Hand, E. S.; Baker, D. C. Synthesis 1989, 905-908. The isolation of 9 by the literature procedure was very complicated, in that it included repeated extractions, repeated distillations, treatment with sulfuric acid and sodium hydroxide, and steam distillation. In our hands, the reported yield of 70% was difficult to obtain after these operations. To improve upon these complicated procedures, following the thermolysis of compound 8, the reaction mixture was directly treated with 50% hydrogen peroxide and trifluoroacetic acid to give 2-chloro-5-fluoropyridine-N-oxide (10), which was easily isolated, with a total yield of 73%. Nitration of 10, followed by catalytic hydrogenation of the resulting 2-chloro-5-fluoro-4-nitropyridine-1-oxide (11) removed the N-oxide function, as well as reduced the nitro group to give the desired 4-amino-2-chloro-5-fluoropyridine (12). N-Oxidation of commercially available 2,5-dichloropyridine (13), followed by nitration and reduction yielded 4-amino-2,5-dichloropyridine (16). Synthesis 1989, 905-908 extractions with sulfuric acid and sodium hydroxide, and steam distillation to obtain after these operations

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-5-fluoropyridine-N-oxide (10, 3.5 g, 23.7 mmol) was gradually added to 46 mL of concentrated sulfuric acid, followed by 10 g of potassium nitrate with stirring. The reaction mixture was heated at 120° C. for 2 h, cooled and poured onto 160 g of crushed ice. The solution was neutralized by dropwise addition of 28% ammonium hydroxide with stirring, while the temperature was maintained below 15° C. with an ice bath. The light yellow crystals which precipitated were collected by filtration, washed with ice water, and dried to yield 2.7 g (59%) of product. A small sample was purified by silica gel column chromatography (CH2Cl2/EtOAc, 4:1, v/v, Rf 0.71): mp 131-132° C.; 1H NMR (DMSO-d6) δ8.70 (m, 1 H, 3-H), 9.12 (m, 1 H, 6-H). Analysis calculated for C5H2ClFN2O3: C, 31.19; H, 1.05; N, 14.55. Found: C, 31.36; H, 1.16; N, 14.75. cooled with stirring, while the temperature was maintained below 15° C. with an ice bath The light yellow crystals which precipitated were collected by filtration washed with ice water dried

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

実験手順: 2-Chloro-5-fluoropyridine (9), a highly volatile substance, was synthesized from thermolysis of 2-chloro-5-pyridinediazonium tetrafluoroborate (8). Hand, E. S.; Baker, D. C. Synthesis 1989, 905-908. The isolation of 9 by the literature procedure was very complicated, in that it included repeated extractions, repeated distillations, treatment with sulfuric acid and sodium hydroxide, and steam distillation. In our hands, the reported yield of 70% was difficult to obtain after these operations. To improve upon these complicated procedures, following the thermolysis of compound 8, the reaction mixture was directly treated with 50% hydrogen peroxide and trifluoroacetic acid to give 2-chloro-5-fluoropyridine-N-oxide (10), which was easily isolated, with a total yield of 73%. Nitration of 10, followed by catalytic hydrogenation of the resulting 2-chloro-5-fluoro-4-nitropyridine-1-oxide (11) removed the N-oxide function, as well as reduced the nitro group to give the desired 4-amino-2-chloro-5-fluoropyridine (12). N-Oxidation of commercially available 2,5-dichloropyridine (13), followed by nitration and reduction yielded 4-amino-2,5-dichloropyridine (16). was easily isolated, with a total yield of 73% removed the N-oxide function

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

実験手順: 2-Chloro-5-fluoropyridine (9), a highly volatile substance, was synthesized from thermolysis of 2-chloro-5-pyridinediazonium tetrafluoroborate (8). Hand, E. S.; Baker, D. C. Synthesis 1989, 905-908. The isolation of 9 by the literature procedure was very complicated, in that it included repeated extractions, repeated distillations, treatment with sulfuric acid and sodium hydroxide, and steam distillation. In our hands, the reported yield of 70% was difficult to obtain after these operations. To improve upon these complicated procedures, following the thermolysis of compound 8, the reaction mixture was directly treated with 50% hydrogen peroxide and trifluoroacetic acid to give 2-chloro-5-fluoropyridine-N-oxide (10), which was easily isolated, with a total yield of 73%. Nitration of 10, followed by catalytic hydrogenation of the resulting 2-chloro-5-fluoro-4-nitropyridine-1-oxide (11) removed the N-oxide function, as well as reduced the nitro group to give the desired 4-amino-2-chloro-5-fluoropyridine (12). N-Oxidation of commercially available 2,5-dichloropyridine (13), followed by nitration and reduction yielded 4-amino-2,5-dichloropyridine (16). Synthesis 1989, 905-908 extractions with sulfuric acid and sodium hydroxide, and steam distillation to obtain after these operations