Hydrogen Bromide → Ethyl 5-bromo-2-methylbenzoate

Participants

Reaction Conditions

Reaction Steps

A mixture of ethyl 5-amino-2-methylbenzoate (1.50 g, 8.3 mmol) in 48% HBr (12 mL) and water (24 mL) was cooled with an ice-bath for 15 min. Sodium nitrite (0.59 g, 8.6 mmol) was then added dropwise as a solution in water (2 mL), and the resulting mixture stirred for 5 min. After this time, the mixture was added to an ice-cold mixture of copper (I) bromide (1.40 g, 9.90 mmol) in 48% HBr (5 mL) and water (12 mL). The resulting mixture was heated to 70° C. for 1 h. After this time, the reaction mixture was cooled to room temperature and diluted with diethyl ether (150 mL). The organic layer was washed with 1 N hydrochloric acid (50 mL), water (50 mL), and brine (50 mL) then dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash chromatography (silica, gradient 1-10%, hexanes/ethyl acetate) afforded 1.4 g (69%) of ethyl 5-bromo-2-methylbenzoate as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 8.03 (d, J=2.2 Hz, 1H), 7.50 (dd, J=8.2, 2.2 Hz, 1H), 7.12 (dd, J=8.2 Hz, 1H), 4.36 (q, J=7.1 Hz, 2H), 2.54 (s, 3H), 1.40 (t, J=7.2 Hz, 3H); ESI MS m/z 404 [M+H]+.

Provenance & Evidence