Hydrochloric Acid → methyl 2-hydroxy-4-(trifluoromethyl)benzoate

Temperature

80 °C

2-Hydroxy-4-(trifluoromethyl)benzoic acid (5.0 g, 24.26 mmol), hydrochloric acid (0.2 mL, 2.40 mmol), sulfuric acid (1.5 mL, 28.1 mmol) and methanol (40 mL) were mixed together and the reaction mixture was stirred at 80° C. over night. The mixture was concentrated and reloaded, stirred at 100° C. overnight. More H2SO4 was added (heated to 100° C. overnight). The mixture was concentrated and ether was added. The organic layer was washed with water twice, saturated solution of bicarbonate then brine, dried over Na2SO4, filtered and concentrated. The residue was dissolved in 20 ml Et2O and filtered (to remove starting material) and the filtrate was evaporated to afford title compound 58 (3.9 g, 73%) as a clear oil.

1. concentrationThe mixture was concentrated
2. stirringstirred at 100° C. overnight
3. additionMore H2SO4 was added
4. temperature(heated to 100° C. overnight)
5. concentrationThe mixture was concentrated
6. additionether was added
7. washThe organic layer was washed with water twice
8. dry with materialsaturated solution of bicarbonate then brine, dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. dissolutionThe residue was dissolved in 20 ml Et2O
12. filtrationfiltered
13. custom(to remove starting material)
14. customthe filtrate was evaporated

ORD record

ord-bd35679633dc46d38c9fdabf2fd19ab2

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193749B2