Ammonium Chloride → Methyl 3-Amino-5-bromo-2-methylbenzoate

Temperature

80 °C

To a stirred solution of methyl 5-bromo-2-methyl-3-nitrobenzoate (290 g, 1058 mmol) in ethanol (1.5 L) was added aqueous ammonium chloride (283 g, 5290 mmol dissolved in 1.5 L water). The resulting mixture was stirred at 80° C. to which iron powder (472 g, 8451 mmol) was added in a portion wise manner. The resulting reaction mixture was heated at 80° C. for 12 h. Upon completion as determined by TLC, the reaction mixture was hot filtered over Celite® and the celite bed was washed with methanol (5 L) followed by washing with 30% MeOH in DCM (5 L). The combined filtrate was concentrated in-vacuo, the residue obtained was diluted with aqueous sodium bicarbonate solution (2 L) and extracted with ethyl acetate (5 L×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the title compound as a solid (220 g, 85%). The compound was taken directly into the next step. 1H NMR (CDCl3, 400 MHz) δ 7.37 (s, 1H), 6.92 (s, 1H), 3.94 (s, 3H), 3.80 (bs, 2H), 2.31 (s, 3H).

1. additionwas added in a portion wise manner
2. customThe resulting reaction mixture
3. filtrationthe reaction mixture was hot filtered over Celite®
4. washthe celite bed was washed with methanol (5 L)
5. washby washing with 30% MeOH in DCM (5 L)
6. concentrationThe combined filtrate was concentrated in-vacuo
7. customthe residue obtained
8. extractionextracted with ethyl acetate (5 L×3)
9. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure

ORD record

ord-6cd8f74092224aae812717bf5ff09072

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765732B2