2-Fluoro-3-nitrotoluene

Clear light yellow to yellow liquid

Compound 2a-1: 2-Fluoro-1-methyl-3-nitrobenzene; [Show Image] Cesium fluoride (97.5 g, 642 mmol) was added under nitrogen atmosphere to a solution of 2-chloro-1-methyl-3-nitrobenzene (73.4 g, 428 mmol) in DMSO (185 mL), and the mixture was stirred at 140°C for 10 hours. The reaction mixture was then poured into 0.5N hydrochloric acid and extracted twice with ethyl acetate. The organic extract was washed with saturated saline and dried over magnesium sulfate. A crude product was obtained by vacuum concentration, and then purified by reduced-pressure distillation (boiling point: 118 °C to 122°C/ 15 mm Hg) to yield the title compound (54.4 g, 82percent) as a yellow oil. 2-Fluoro-1-methylCesium fluoride (97.5 g, 642 mmol) was added under nitrogen atmosphere to a solution of 2-chloro-1-methyl-3-nitrobenzene(73.4 g, 428 mmol) in DMSO (185 mL), and the mixture was stirred at 140° C. for 10 hours. The reaction mixture was then poured into 0.5N hydrochloric acid and extracted twice with ethyl acetate. The organic extract was washed with saturated saline and dried over magnesium sulfate. A crude product was obtained by vacuum concentration, and then purified by reduced-pressure distillation (boilingpoint: 118° C. to 122° C./15 mm Hg) to yield the title compound (54.4 g, 82percent)as a yellow oil.Under the atmosphere of nitrogen, a solution of 5-bromo-2-amino-aniline (10.0 g, 57.8 mmol) in tetrahydrofuran(200 ml) was placed in a 500 ml three-neck flask, the solution was cooled to 0C in a dry ice bath. Sodium hydrogen(3.47 g, 86.7 mmol, purity: 60%) was added into the reaction solution batchwise. After stirring for half an hour, a solutionof 2-fluoro-3-methylnitroaniline (13.5 g, 86.7 mmol) in tetrahydrofuran (5.0 ml) was dropwise added into the reactionsolution slowly. Upon the completion of the dropwise addition, the reaction was warmed to 25C and stirred for 16 hours.When LCMS detection showed that most of the raw materials have been reacted completely, water (40 ml) was addedinto the reaction solution to quench the reaction, and then the mixture was extracted with ethyl acetate (2350 ml). Theorganic phases were combined and extracted with saturated saline (100 ml), dried over anhydrous sodium sulfate, andfiltered. The filtrate was concentrated at reduced pressure to give a crude product, which was purified over a flash silicagel column (mobile phase: 0-15% ethyl acetate/petroleum ether) to give the Example 10D (10.0 g, yield: 56.3%) as ayellow solid. LCMS (ESI) m/z: 307.8, 309.8 [M+1]+ 1H NMR (400MHz, CHLOROFORM-d) delta 8.21 (d, J = 2.4 Hz, 1H), 7.98 (br. s., 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.60 (dd, J = 8.8, 2.4 Hz, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.23 (t, J = 8.0 Hz, 1H), 6.48 (d, J = 8.4 Hz, 1H), 2.27-2.20 (m, 3H).

Molecular Weight:155.13
XLogP3:2.2
Hydrogen Bond Acceptor Count:3
Exact Mass:155.03825660
Monoisotopic Mass:155.03825660
Topological Polar Surface Area:45.8
Heavy Atom Count:11
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes