Water → Methyl 3-Amino-5-bromo-2-methylbenzoate

Temperature

70 °C

To a solution of methyl 5-bromo-2-methyl-3-nitrobenzoate (6.3 g, 21 mmol) in methanol (150 ml) was added ammonium chloride (11.0 g, 209 mmol) followed by deionized water (75 ml). The mixture was heated to 70° C. before the addition of iron (7.0 g, 125 mmol). The reaction mixture was stirred at 70° C. for 2 hours, before being allowed to cool to room temperature and filtered through Kieselgel. The filter pad was washed with MeOH (150 ml) and the filtrate concentrated in-vacuo. The residue was dissolved in saturated NaHCO3 (aq) (50 ml) and EtOAc (150 ml). The phases were separated and the organic phase was washed with saturated NaHCO3 (aq) (3×50 ml), dried over MgSO4, filtered and concentrated in-vacuo. The residue was purified by flash column chromatography (50 g silica Isolute cartridge, 5-20% EtOAc:Heptanes) to give the title compound (3.0 g, 51%) as a thick pale yellow oil. LC-MS 87%, 1.89 min (3.5 minute LC-MS method), m/z=243.9, 244.9, 245.9, 246.9; 1H NMR (500 MHz, Chloroform-d) δ ppm 7.34 (d, J=1.89 Hz, 1H) 6.95 (d, J=1.89 Hz, 1H) 3.88 (s, 3H) 3.80 (br. s., 2H) 2.29 (s, 3H).

1. temperatureto cool to room temperature
2. filtrationfiltered through Kieselgel
3. washThe filter pad was washed with MeOH (150 ml)
4. concentrationthe filtrate concentrated in-vacuo
5. dissolutionThe residue was dissolved in saturated NaHCO3 (aq) (50 ml)
6. customThe phases were separated
7. washthe organic phase was washed with saturated NaHCO3 (aq) (3×50 ml)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated in-vacuo
11. customThe residue was purified by flash column chromatography (50 g silica Isolute cartridge, 5-20% EtOAc:Heptanes)

ORD record

ord-36fb0d6a6e0f44a5b7a3da504627120d

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765732B2