Methyl 3-Amino-6-bromopyrazine-2-carboxylate → Methyl 6-bromo-3-oxo-3,4-dihydropyrazine-2-carboxylate

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Reaction Conditions

Reaction Steps

Concentrated sulphuric acid (5 ml) was stirred and cooled to 2-5° C. and sodium nitrite (0.7 g) added batchwise such that the reaction exotherm did not exceed 10° C. The reaction mixture was allowed to reach room temperature and then warmed to 40° for 2-3 minutes to give a homogeneous solution. The stirred reaction mixture was then cooled to 2°-5° C. and a cooled (2°-5° C.) solution of 2-amino-3-methoxycarbonyl-5-bromopyrazine (JACS, 1949, 71, 2798; 2.32 g) in concentrated sulphuric acid added dropwise so that the reaction temperature did not exceed 5° C. After the addition was complete, the reaction mixture was allowed to warm to 15° C. over three hours and then added dropwise to crushed ice (200 g). The resulting mixture was extracted with ethyl acetate. The organic phase washed with brine, dried with sodium sulphate and evaporated under reduced pressure to give the crude product as a yellow solid. The crude product was used in further experiments without further purification. A portion of the crude product was recrystallised from acetonepetroleum ether (boiling range 60°-80° C.) to give 3-methoxycarbonyl-5-bromopyrazine-2-one as a yellow solid:

Provenance & Evidence