Nitric Acid → 2-Amino-4-methyl-5-nitropyridine

Temperature

0 °C

Concentrated sulfuric acid (120 mL) was cooled in an ice bath at 0° C. 2-Amino-4-methylpyridine (25.0 g, 230=mol) was added portionwise. A mixture of concentrated sulfuric acid (18 mL) and concentrated nitric acid (17.5 mL) was added with addition funnel over 1 h, maintaining the temperature at 0° C. The reaction mixture was then warmed to room temperature over 4 h. After 15 h, the reaction mixture was heated at 60° C. for 1 h, and then at 100° C. for 1 h. The reaction mixture was poured over ice and adjusted to pH 4-5 with 6 N aqueous sodium hydroxide. The 3-regioisomer was removed by steam distillation (9.11 g, 26%). The remaining residue was extracted with methylene chloride and dried over sodium sulfate, and the solvent was evaporated. The dark yellow solid was crystallized from acetonitrile and methanol to give 2-amino-4-methyl-5-nitropyridine (9.53 g, 27%) as a dark yellow solid: 1H NMR (300 MHz, CD3OD) δ2.53 (3H, s), 6.39 (1H, s), 8.76 (1H, s).

1. additionwas added with addition funnel over 1 h
2. temperatureThe reaction mixture was then warmed to room temperature over 4 h
3. temperaturethe reaction mixture was heated at 60° C. for 1 h
4. waitat 100° C. for 1 h
5. additionThe reaction mixture was poured over ice
6. customThe 3-regioisomer was removed by steam distillation (9.11 g, 26%)
7. extractionThe remaining residue was extracted with methylene chloride
8. dry with materialdried over sodium sulfate
9. customthe solvent was evaporated
10. customThe dark yellow solid was crystallized from acetonitrile and methanol

ORD record

ord-1c3697b4ad5d4653b1ffc7daa9d2e903

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07608627B2