Methyl3-bromo-5-nitrobenzoate

Methyl 3-bromo-5-nitrobenzoate 51) methyl 3-nitrobenzoate (50) (85.4 g; 471 mmol, 1 eq.) were dissolved in concentrated sulfuric acid (500 mL). Then a solution of dibromoisocyanuric acid (67.6 g; 235 mmol, 0.5 eq.) in concentrated sulfuric acid (850 mL) was added. After stirring the clear solution for 2 hours the whole mixture were poured on 5 kg ice. The slurry was extracted 5 times with each 2 L of dichloromethane. The combined organic phases were dried over sodium sulfate. After evaporating of the solvent the crude product were recrystallized- from methanol to yield the title compound (105.8 g 406 mmol, 86percent) as large pale yellow crystals. RTo a solution of 60 (1.0 g, 4.1 mmol) in MeOH (30 mL) was added dropwise H2S04 (5 mL). The reaction was refluxed overnight before concentrated. The residue was treated with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over Na2SO4 and evaporated under reduced pressure togive 61(1.1 g, 100percent) as an off-white solid. A suspension of 61(900 mg, 3.46 mmol), 1 (853 mg, 10.4 mmol), K2C03 (955 mg, 6.92 mmol), Cul (198 mg, 1.04 mmol) and 8- hydroxyquinoline (100 mg, 0.69 mmol) in DMSO (9 mL) was heated at 110 °C overnight under nitrogen. After cooling, water was added and the mixture was acidified by aqueous KHSO4, and extracted with EtOAc 3 times. The product was in the waterphase. The water layer was directly purified by reverse prep-HPLC to give 62 (310 mg, 36percent) as a white solid. LCMS (m/z: m+1): 248.1.3-Bromo-5-nitrobenzoic acid (5.87 g, 23.6 mmol; 1 equiv), which was obtained by bromination of nitrobenzoic acid according to the protocol of 9, was dissolved in methanol (100 mL) and a few drops of HTo a solution of 3-bromo-5-nitro-benzoic acid (D5) (22.3 g, 90.6 MMOL, 1 equiv) in MEOH (300 ml) at 0°C was added SOCI2 (7.9 ML, 108 mmol, 1.2 equiv) dropwise. The resulting solution was stirred at reflux for 4 hours then cooled to room temperature and concentrated in vacuo. The residue was diluted with AcOEt, washed twice with 2N aqueous NAOH solution and once with brine, dried over MGS04 and concentrated in vacuo to give 3-bromo-5-nitro-benzoic acid methyl ester (D11) (22.1 g, 94percent) as a pale brown solid. RT = 3.18 min; Description 11 (Alternative Procedure) 3-Bromo-5-nitro-benzoic acid methyl ester (D11) To an ice cold solution of 3-bromo-5-nitro-benzoic acid (D5) (2.5 g, 10 mmol, 1 equiv) in MEOH (25 mi) was added SOCS (1 ml, 15 mmol, 1.5 equiv) dropwise. The resulting solution was allowed to warm to room temperature and was then stirred at 60°C for 3 h, cooled to room temperature and concentrated IN VACUO. The residue was dissolved in AcOEt and the organic layer was washed with saturated aqueous NAHC03 solution, dried over MGS04 and concentrated in vacuo to give 3-bromo-5-nitro-benzoic acid methyl ester (D11) (2.6 g, 100percent) as a yellow solid. RT = 3.22 min

Molecular Weight:260.04
XLogP3:2.7
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:258.94802
Monoisotopic Mass:258.94802
Topological Polar Surface Area:72.1
Heavy Atom Count:14
Complexity:240
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes