Benzoic acid，4-fluoro-2,6-dimethyl-， methyl ester

General procedure: To a 250 mL round bottom flask equipped with a stir barwere added 2, 4, 6-trimethylbenzoic acid (6.57 g, 40.0 mmol, 1 equiv), potassium carbonate (8.29g, 60.0 mmol, 1.5 equiv) and DMF (50 mL). Iodomethane (3.00 mL, 48.0 mmol, 1.2 equiv) wasslowly added to the reaction vessel and the resulting suspension was stirred vigorously at roomtemperature for 24 h. The reaction was poured onto 300 mL of H2O and extracted with 3 x 300mL portions of Et2O. The combined organic extracts were washed with 3 x 150 mL portions ofH2O and 2 x 150 mL portions of brine. The organic layer was dried over MgSO4, filtered, andconcentrated to dryness. The residue was purified by passing through a pad of silica eluting with1:1 EtOAc/hexanes to give methyl ester S4 (6.28 g, 35.2 mmol, 88% yield) as a pale yellow oil.Spectral data are in agreement with those previously published.44-Amino-2, 6-dimethyl benzoic acid (200 mg, 1.1 mmol) and NOBF4 (196 mg, 1.7 mmol) were heated in 1, 2-dichlorobenzene at 100 C for 30 min. The solution was cooled and diluted with MeOH and water. A few pellets (2-3) of KOH were added, and the solution was heated at reflux for 16 h. The solution was concentrated. The residue was partitioned between Et2O and 1 N NaOH. The aqueous layer was extracted with Et2O. The aqueous layer was cooled to 0 C and acidified with conc. HCl (pH = 1-2). The aqueous layer was extracted with CH2Cl2. The organic layers were dried (Na2SO4). Filtration and concentration gave 58 mg (31 %) of the acid as a tan solid.4-Amino-2, 6-dimethyl benzoic acid (200 mg, 1.1 mmol) and NOBF4 (196 mg, 1.7 mmol) were heated in 1, 2-dichlorobenzene at 100 C. for 30 min. The solution was cooled and diluted with MeOH and water. A few pellets (2-3) of KOH were added, and the solution was heated at reflux for 16 h. The solution was concentrated. The residue was partitioned between Et2O and 1 N NaOH. The aqueous layer was extracted with Et2O. The aqueous layer was cooled to 0 C. and acidified with conc. HCl (pH=1-2). The aqueous layer was extracted with CH2Cl2. The organic layers were dried (Na2SO4). Filtration and concentration gave 58 mg (31%) of the acid as a tan solid.4-Amino-2, 6-dimethyl benzoic acid (200 mg, 1.1 mmol) and NOBF4 (196 mg, 1.7 mmol) were heated in 1, 2-dichlorobenzene at 100 C. for 30 min. The solution was cooled and diluted with MeOH and water. A few pellets (2-3) of KOH were added, and the solution was heated at reflux for 16 h. The solution was concentrated. The residue was partitioned between Et2O and 1 N NaOH. The aqueous layer was extracted with Et2O. The aqueous layer was cooled to 0 C. and acidified with conc. HCl (pH=1-2). The aqueous layer was extracted with CH2Cl2. The organic layers were dried (Na2SO4). Filtration and concentration gave 58 mg (31%) of the acid as a tan solid.4-Amino-2, 6-dimethyl benzoic acid (200 mg, 1.1 mmol) and NOBF4 (196 mg, 1.7 mmol) were heated in 1, 2-dichlorobenzene at 100 C for 30 min. The solution was cooled and diluted with MeOH and water. A few pellets (2-3) of KOH were added, and the solution was heated at reflux for 16 h. The solution was concentrated. The residue was partitioned between Et2O and 1 N NaOH. The aqueous layer was extracted with Et2O. The aqueous layer was cooled to 0 C and acidified with conc. HCl (pH = 1-2). The aqueous layer was extracted with CH2Cl2. The organic layers were dried (Na2SO4). Filtration and concentration gave 58 mg (31 %) of the acid as a tan solid.