Benzoic acid, 5-fluoro-2-methyl-3-nitro-, methyl ester

General procedure: To a solution of 2-Methyl-3-nitrobenzoic acid 12 or 5-fluoro-2-methyl-3-nitrobenzoic acid 13 (552 mmol) in methanol was added sulfoxide chloride (1100 mmol) dropwise below 0 C during 10 min with stirring. The mixture was heated to reflux for 4~5 h and then drop into 900ml ice-water with stirring. The precipitate was collected by filtration and dried to give corresponding products.Step A 5-fluoro-2-methyl-3-nitrobenzoic acid crude product (7.0g) was dissolved in methanol (70mL), was added 98percent sulfuric acid (2mL). The mixture was stirred overnight at 70 °C. After the reaction mixture was concentrated, water was added (50mL) and ethyl acetate (150 mL) separated, the aqueous phase extracted with ethyl acetate (100mL × 2). The combined organic phase was washed once with brine (30 mL), dried over anhydrous sodium sulfate, filtered, and spin dry the solvent, column chromatography (PE:EtOAc = 10:1 ~ 3:1) to give a pale yellow solid 5-fluoro-2-methyl-3-nitrobenzoic acid methyl ester (3.5g, 42percent for two steps).8.56 g (42.99 mmol) of 2-methyl-5-fluoro-3-nitrobenzoic acid is added in 76 ml of N, N-dimethylformamide and mixed with 9.15 g (64.48 mmol) of methyl iodide and 8.91 g (64.48 mmol) of potassium carbonate. Example 63AMethyl 5-fluoro-2-methyl-3-nitrobenzoate[00597] To a solution of cone. HTo a solution of 5-fluoro-2-methyl benzoic acid (62.6 g, 406 mmol) in CONC. sulfuric acid (500 ml) cooled at-10 °C was added dropwise a mixture of fuming nitric acid (20.6 ml) and CONC. sulfuric acid (94 ml). After complete addition the mixture was stirred at 0 °C for 1 hour. Poured onto ice/water (1. 5 1) and stirred for 10 minutes then extracted with EtOAc (3 x 500 ml), the combined EtOAc layers were washed with water (800 ml), saturated NaCl (500 ML), dried over NA2SO4, filtered and evaporated. The residue was dissolved in methanol (1 1) and conc. HC1 (15 ml) added, and the resulting mixture heated at reflux overnight. The cooled reaction mixture was evaporated and the residue partitioned between DCM (700 ml) and saturated NAHC03, the organic layer was separated and washed with saturated NACL (200 ML), dried OVER NA2S04, filtered and evaporated to give the title compound (51.5 g, 59percent) as an oil.step 2: Compound 2 (19.5 g, 0.1 mol) was dissolved in 80 mL of acetic acid and 50 mL of acetic anhydride, and the temperature was lowered to 10 ° C. Potassium nitrate (15.2 g, 0.15 mol) was added in portions, and after the addition, the reaction was carried out for 6 h. The insoluble material was removed by filtration, and the reaction mixture was poured into 400 mL of ice water, filtered, and dried to give 17.3 g of Compound 3.

Molecular Weight:213.16
XLogP3:2.1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:213.04373590
Monoisotopic Mass:213.04373590
Topological Polar Surface Area:72.1
Heavy Atom Count:15
Complexity:265
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes