Methyl iodide → Methyl 4-bromo-2-nitrobenzoate

Temperature

0 °C

Methyl 2-amino-4-bromobenzoate. To a stirred solution of 4-bromo-2-nitrobenzoic acid (3.8 g, 15 mmol) in DMF (30 mL) at 0° C. was added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (10.0 mL, 75.0 mmol) followed by iodomethane (4.7 mL, 75 mmol). The reaction mixture was stirred 15 min at 0° C., then was allowed to warm to room temperature and was stirred overnight. The mixture was poured into H2O and extracted with EtOAc (2×). The combined organic extracts were washed with H2O (2×), dried (MgSO4), and concentrated in vacuo. The residue was purified by flash chromatography (hexanes/EtOAc) to afford methyl 4-bromo-2-nitrobenzoate as a pale yellow solid (3.52 g, 90%). To a solution of the nitrobenzoate (3.52 g, 13.5 mmol) in 1:1 EtOAc/DCM (30 mL) at room temperature was added SnCl2.2H2O (15 g, 67 mmol). The reaction mixture was allowed to stir overnight. The solvents were evaporated in vacuo, and the residue was partitioned between satd. aq. NaHCO3 and DCM. The layers were separated, and the aqueous layer was further extracted with DCM (2×). The combined organic layers were dried (MgSO4) and concentrated in vacuo to provide the pure aminobenzoate as a white solid (2.89 g, 93%). 1H NMR (400 MHz, CDCl3): 7.70 (d, J=8.6 Hz, 1H), 6.84 (d, J=1.9 Hz, 1H), 6.75 (dd, J=8.6, 1.9 Hz, 1H), 5.78 (br s, 2H), 3.86 (s, 3H).

1. temperatureto warm to room temperature
2. stirringwas stirred overnight
3. extractionextracted with EtOAc (2×)
4. washThe combined organic extracts were washed with H2O (2×)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash chromatography (hexanes/EtOAc)

ORD record

ord-2f9f8b7c8eb648f0a1e40a7c0eddbed2

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07563895B2