4-Bromo-2-nitrobenzoate tert-butyl ester can be used as a pharmaceutical synthesis intermediate. It can be prepared by reacting 4-bromo-2-nitrobenzoic acid with 2-bromo-2-methylpropane. It can be used to prepare the compound 2-amino-4-bromobenzoate tert-butyl ester, which can also be widely used as a pharmaceutical synthesis intermediate.
To a solution containing 5.0 g of 4-bromo-2-nitrobenzoic acid 50 mL of N,N-dimethylacetamide was added 41 g of potassium carbonate, 4.6 g of benzyltriethylammonium chloride, and 69 mL of 2-bromo-2-methylpropane and stirred at 55 C for 10 hours. After the reaction mixture was cooled to room temperature, 12 mL of 2-bromo-2-methylpropane was added and stirred at 55C for 4 hours. After cooling the reaction mixture to room temperature, water and ethyl acetate were added. The organic layer was separated and washed with 10% aqueous citric acid and saturated aqueous sodium chloride in turn, then dried with anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. Methanol was added to the obtained residue and 3.0 g of tert-butyl 4-bromo-2-nitrobenzoate was obtained as a white solid by filtration and separation of solids.1H-NMR (CDCl3) : 1.55 (9H, s), 7.63 (1H, d, J = 8.3 Hz), 7.77 (1H, dd, J = 8.3, 1.9 Hz), 7.95 (1H, d , J = 1.9 Hz).
