Hydrogen Bromide → Ethyl 2-bromothiazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

The starting material can be prepared as follows: To a 500 mL 24/40 3-neck round bottom flask equiped with a mechanical stirrer, was charged 3.4 g (19.7 mmol) of 2-amino-5-thiazolecarboxylic acid ethyl ester (Ber., 1888, 21, 938), partially dissolved in 30 mL of concentrated phosphoric acid. The stirring mixture was cooled in an ice bath and then 9 mL of concentrated nitric acid was added slowly, followed by the dropwise addition of 2.85 g (41.3 mmol) of sodium nitrite in 5 mL of water. The mixture was stirred in the cold for 35 minutes, and then added dropwise was 3.0 g (47.2 mmol) of copper powder in 75 mL of 48% hydrobromic acid cooled to -10° C. After the evolution of nitrogen gas ceased, the thick reaction mixture was removed from the ice bath and neutralized to pH 8, first using 5N sodium hydroxide and then sodium carbonate. The aqueous was then extracted with 400 mL ether. The insoluble material was filtered away and the filtrate was washed with 5% sodium bicarbonate, water, dried over sodium sulfate, and removed in vacuo. The crude residue was then purified using silica gel flash chromatography eluting with 1:1 ether/hexanes to give 2.4 g (52%) of 2-bromo-5-thiazolecarboxylic acid ethyl ester as a yellow oil. Rf =0.62 (1:1 ether/hexanes). 1H NMR (300 MHz, DMSO d6) δ 1.26 (t, J=7.0 Hz, 3H), 4.29 (q, J=7.1 Hz, 2H), 8.28 (s, 1H).

Provenance & Evidence