Hydrogen Bromide → Ethyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of sodium nitrite (8.56 g, 124 mmol) in 20 mL of H2O was added over a 30 minute period to a mixture of the aminothiazole (7.44 g, 40 mmol), 85% phosphoric acid (50 mL) and 70% nitric acid (25 mL) at −10° C. The mixture began to bubble immediately and an exotherm was observed. A CO2/acetone bath was used to maintain the temperature at −10° C. throughout the addition. An orange precipitate formed and the mixture became very difficult to stir. Once the addition was complete, the mixture was allowed to warm to room temperature and stirred for ˜20 minutes. The reaction mixture was then poured into a mixture of hydrobromic acid (20 mL) and cuprous bromide (5.74 g, 40 mmol). After vigorous gas evolution, the mixture was diluted with H2O (650 mL) and filtered to yield a brown solid. The solid was dissolved in ethyl acetate and concentrated onto ˜100 g of silica gel and chromatographed over silica gel, eluting with a serial dilution of hexane to 90% hexane/10% ethyl acetate. Isolation of the major product gave 1.92 g (19% yield) of the desired product as a yellow solid: mp 63-65° C.; 1H NMR (CDCl3) δ4.35 (q, 2H), 2.7 (t, 3H), 1.35 (t, 3H).

Provenance & Evidence