Hydrogen Bromide → Ethyl 5-bromo-2-methylbenzoate

Temperatur

70 °C

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]+.

1. temperaturewas cooled with an ice-bath for 15 min
2. temperatureAfter this time, the reaction mixture was cooled to room temperature
3. washThe organic layer was washed with 1 N hydrochloric acid (50 mL), water (50 mL), and brine (50 mL)
4. dry with materialthen dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customPurification by flash chromatography (silica, gradient 1-10%, hexanes/ethyl acetate)

ORD-Eintrag

ord-aea5a402265244a4a14ccfeece4e83b0

Quelldatensatz

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08110681B2