2-Bromopropane → 3,4-Diisopropoxy-5-(trifluoromethyl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

2-Bromopropane (380 μL, 4.05 mmol) was added to a suspension of 3,4-dihydroxy-5-(trifluoromethyl)benzoic acid (5) (257 mg, 1.16 mmol) and K2CO3 (560 mg, 4.05 mmol) in DMF (10 mL) and the reaction mixture was stirred at 80° C. for 20 h. The reaction mixture was diluted with EtOAc (30 mL) and washed sequentially with 1M HCl (30 mL) and brine (5×30 mL), and then the solvent was removed in vacuo. The residue was suspended in 2M sodium hydroxide (5.8 mL, 12 mmol) and the mixture was stirred at 80° C. for 4 h. Dioxane (10 mL) was added and the mixture continued to stir at 80° C. for a further 20 h. The solvents were removed in vacuo and the residue was partitioned between EtOAc (50 mL) and 1M HCl (50 mL). The phases were separated and the organic solution was washed with brine (3×40 mL), and then dried over MgSO4, and filtered. The solvent was removed in vacuo and the residue was purified by silica chromatography (40 g, 0-15% MeOH in DCM) to afford 3,4-diisopropoxy-5-(trifluoromethyl)benzoic acid (6) (118 mg, 33%) as a yellow solid.

Provenance & Evidence