Methyl iodide → Methyl 5-bromo-2-methyl-3-nitrobenzoate

Temperature

60 °C

To a stirred solution of 5-bromo-2-methyl-3-nitrobenzoic acid (285 g, 1105 mmol) in DMF (2.8 L) at room temperature was added sodium carbonate (468 g, 4415 mmol) followed by addition of methyl iodide (626.6 g, 4415 mmol). The resulting reaction mixture was heated at 60° C. for 8 h. After completion (monitored by TLC), the reaction mixture was filtered (to remove sodium carbonate) and washed with ethyl acetate (1 L×3). The combined filtrate was washed with water (3 L×5) and the aqueous phase was back extracted with ethyl acetate (1 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 (290 g, 97% yield). The isolated compound was taken directly into the next step. 1H NMR (CDCl3, 400 MHz) δ 8.17 (s, 1H), 7.91 (s, 1H), 3.96 (s, 3H), 2.59 (s, 3H).

1. customThe resulting reaction mixture
2. filtrationAfter completion (monitored by TLC), the reaction mixture was filtered
3. custom(to remove sodium carbonate)
4. washwashed with ethyl acetate (1 L×3)
5. washThe combined filtrate was washed with water (3 L×5)
6. extractionthe aqueous phase was back extracted with ethyl acetate (1 L×3)
7. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure

ORD record

ord-01aef388e52348589d0ddd5a519fb5f7

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765732B2