Acetic Acid → 3-Amino-6-chloro-4-picoline

Participants

Reaction Conditions

Reaction Steps

2-Chloro-4-methyl-5-nitropyridine (1 g, 5.8 mmol) was dissolved in EtOH (60 mL). AcOH (4 mL) and Fe (5 eq.) were added and the mixture was refluxed at 80° C. overnight. The mixture was filtered through celite and reduced under vacuum to afford the crude 5-amino-2-chloro-4-methylpyridine which was used in the next step with no further purification. The amine was dissolved in conc. HCl (6 mL), transferred to a 3-neck round bottom flask, and cooled to −5° C. A solution of NaNO2/H2O (440 mgs/5 mL) was slowly added and the mixture was allowed to stir for 10 mins. To a second, separate 3-neck round bottom flask was added H2O (12 mL) and cooled to −5° C. Thionyl chloride (4.5 eq.) was then added dropwise. After complete addition the mixture was allowed to warm to room temp. Whereupon CuCl (0.05 eq.) was added and the mixture was then cooled back down to −5° C. The first reaction mixture, containing the amine precursor, was slowly added to the second reaction mixture. A froth formed and was filtered off to afford 6-chloro-4-methyl-pyridine-3-sulfonyl chloride which was used in the next step with no further purification. The title compound was synthesized from 2-[2-(R,S)-3-oxo-1,2,3,4-tetrahydro-quinoxalin-2-yl]-N-(pyrid-4-yl)ethyl acetamide and 6-chloro-4-methyl-pyridine-3-sulfonyl chloride using Method G.

Provenance & Evidence