Methyl 5-fluoro-2-methyl-3-nitrobenzoate

The Uses of Methyl 5-fluoro-2-methyl-3-nitrobenzoate

Methyl 5-fluoro-2-methyl-3-nitrobenzoate is used in organic synthesis and it is used in the synthesis of 6-Fluoro-4-nitroisobenzofuran-1 (3H)-one.

Preparation

Methyl 5-fluoro-2-methyl-3-nitrobenzoate synthesis: To a solution of conc. H2SO4 (700mL) was added portionwise 5-fluoro-2-methylbenzoic acid (80g, 520 mmol) at -5-0°C. Then a mixture of conc. HNO3(60.4 g. 624 mmol) in conc. H2SO4 (60 mL) was added drop-wise at -5-0°C. in a period of about 1.5 hrs. After the addition, the mixture was stirred at this temperature for 2 hrs. TLC (petroleum ether/ EtOAc=1:1) showed the reaction was complete. The mixture was poured into crash ice with vigorous stirring and the precipitate was collected by filtration. The precipitate was dissolved in EtOAc, washed with brine, dried over anhydrous Na2SO4 concentrated to give crude 5-fluoro-2-methyl-3-nitrobenzoic acid (54 g). A solution of this crude 5-fluoro-2-methyl-3-nitrobenzoic acid (54 g) in dry methanol (500 mL) was cooled to 0°C., SOCl2 (64.52g, 542.3 mmol) was added drop-wise. After the addition, the mixture was heated to reflux for 16hrs. TLC (petroleum ether/EtOAc=1:1) showed the reaction was complete. Solvent was removed under reduced pressure to give crude product. The crude product was purified by silica gel chromatography (petroleum ether to petro leum ether/EtOAc=50: 1) to give methyl 5-fluoro-2-methyl-3-nitrobenzoate (28 g, yield 25% for two steps) as a white solid.