tert-Butyl 2-aMino-5-broMobenzoate

64113-91-3

668969-63-9

The general procedure for the synthesis of tert-butyl 2-amino-5-bromobenzoate from tert-butyl 2-aminobenzoate was as follows: to a stirred and cooled DMF (20 mL) solution of tert-butyl 2-aminobenzoate (23.37 g, 120.9 mmol) was slowly added a N-bromosuccinimide (NBS) (21.50 g, 120.8 mmol) in a 0 °C DMF (20 mL) solution, keeping the temperature at 0°C during the process. After the addition was completed, the NBS vessel was rinsed with an additional 10 mL of DMF and the rinse solution was added to the reaction mixture. The reaction mixture was slowly warmed from 0 °C to room temperature and stirring was continued for 4 hours. Upon completion of the reaction, the reaction mixture was diluted with ethyl acetate (EtOAc, 500 mL) and subsequently washed with 1 N NaOH solution (3 x 300 mL). The organic layer was dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated to dryness. The crude product was adsorbed onto silica gel (48 g) and purified by silica gel column chromatography (620 g silica gel, eluent 80:1, 70:1, then 60:1 heptane/tert-butyl methyl ether (HEPTANE/TBME)). The target fraction was collected and concentrated to give 25.99 g (79% yield) of tert-butyl 2-amino-5-bromobenzoate as a yellow-white solid. The product was confirmed by 1H NMR (300 MHz, CDCl3): δ 7.91 (d, 1H), 7.30 (dd, 1H), 6.53 (d, 1H), 5.72 (br s, 1H), 1.58 (s, 9H).