Methyl iodide → Methyl 5-bromo-2-methoxy-3-methylbenzoate

Temperature

58 °C

To a solution of 5-bromo-2-hydroxy-3-methyl-benzoic acid (3 g, 12.9 mmol, 1.0 eq) and K2CO3 (5.38 g, 38.9 mmol, 3.0 eq) in acetone (15 mL) was added MeI (5.53 g, 38.9 mmol, 3.0 eq). The mixture was stirred at 58° C. overnight. TLC indicated that the reaction was not completed. Water was added and the aqueous layer extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4) filtered and evaporated in vacuo. The crude solid obtained was dissolved in DMF (20 mL) and Cs2CO3 (6 g, 18.4 mmol, 1.4 eq) added. To the mixture was added MeI (2 mL, 38.95 mmol, 3 eq). The mixture was stirred for 1 h at room temperature, water was added and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo to give the title compound as a white solid (2.6 g, 77%).

1. extractionthe aqueous layer extracted with EtOAc
2. extractionThe organic extract
3. washwas washed with water and brine
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. customevaporated in vacuo
7. customThe crude solid obtained
8. stirringThe mixture was stirred for 1 h at room temperature
9. extractionthe aqueous layer was extracted with EtOAc
10. washThe combined organic extracts were washed with water and brine
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. customevaporated in vacuo

ORD record

ord-a137cbb6b8e94faca9e92d005cb5808b

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249085B2