Water → Methyl 3-amino-5-chloro-2-methylbenzoate

Temperature

70 °C

To a solution of methyl 5-chloro-2-methyl-3-nitrobenzoate (9.19 g, 40 mmol) in methanol (200 ml) at room temperature was added ammonium chloride (21 g, 400 mmol) followed by deionized water (100 ml). The mixture was heated to 70° C. before the addition of iron (13.4 g, 240 mmol). The reaction turned to a dark colour over the 2.5 hours it was stirred at 70° C. This mixture was allowed to cool to room temperature and was filtered through Kieselgel. The filter pad was washed with MeOH (100 ml) and the filtrate concentrated under reduced pressure. The residue was dissolved in deionized water (100 ml) and EtOAc (100 ml). The phases were separated and the aqueous phase was extracted with EtOAc (2×100 ml). The combined organic extracts were washed with brine (100 ml), dried over MgSO4, filtered and concentrated under reduced pressure to give 7.6 g of the title compound as a viscous orange oil that solidified upon standing. This material was used without further purification. LC-MS 63%, m/z=200.3/202.0, 1H NMR (500 MHz, Chloroform-d) δ 7.20 (1H, d, J=2.21 Hz), 6.80 (1H, d, J=2.05 Hz), 3.89 (3H, s), 3.74-3.87 (2H, m), 2.30 (3H, s).

1. customturned to a dark colour over the 2.5 hours it
2. temperatureto cool to room temperature
3. filtrationwas filtered through Kieselgel
4. washThe filter pad was washed with MeOH (100 ml)
5. concentrationthe filtrate concentrated under reduced pressure
6. dissolutionThe residue was dissolved in deionized water (100 ml)
7. customThe phases were separated
8. extractionthe aqueous phase was extracted with EtOAc (2×100 ml)
9. washThe combined organic extracts were washed with brine (100 ml)
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure

ORD record

ord-e16d30705fa24f3c893269380d37ff49

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376422B2