Benzoic acid, 2-fluoro-4-nitro-, methyl ester

Step 1 : To a solution of 2-fluoro-4-nitrobenzoic acid (1 g, 5.402 mmol) in MeOH was added H2SO4 (2.9 ml). The reaction mixture was refluxed overnight, and then cooled to room temperature and concentrated. The residue was diluted with EtOAc and washed with a saturated NaHCO3 solution. The organic layer was dried over MgSO4 and concentrated. The crude was purified by column chromatography to afford the pure compound methyl 2-fluoro- 4-nitrobenzoate (1 .05 g, 98 percent).471a) Synthesis of Methyl 2-Fluoro-4-nitrobenzoate.To a 500ml round bottom flask, 2-fluoro-4-nitrobenzoic acid (1 1.68g, 63.1mmoles), toluene (200ml) and methanol (30ml) were added, respectively. Trimethylsillyldiazomethane (2M) in diethyl ether (38ml, 76mmoles) was then added dropwise at romm temperature over 30 minutes. The solution was then stired for lhour. The sovents were then removed under vaccum to afford a yellow solid. The residual solvent was co-evaporated with methanol (100ml) to give 12.52g of yellow solid (100percent yield). NMR lH-(DMSO)-I'-8.28 (d, IH, J=7.58Hz), 8.10-8.22 (m, 2H), 3.93 (s, 3H).Add diazomethane (22.3 mL, 2 M in ether) to a mixture of 2-fluoro-4-nitro benzoic acid (4.14 g) and ether (50 mL). Stir at room temperature overnight. Concentrate under reduced pressure to provide (4.08 g, 92percent) of an oil.Step 1 : To a solution of 2-fluoro-4-nitrobenzoic acid (1 g, 5.402 mmol) in MeOH was added H2SO4 (2.9 ml). The reaction mixture was refluxed overnight, and then cooled to room temperature and concentrated. The residue was diluted with EtOAc and washed with a saturated NaHCO3 solution. The organic layer was dried over MgSO4 and concentrated. The crude was purified by column chromatography to afford the pure compound methyl 2-fluoro- 4-nitrobenzoate (1 .05 g, 98 %).[00309] To a solution of 2-fluoro-4-nitro-benzoic acid A (4.9 g, 26 mmol) in methanol (60 mL) was added hydrogen chloride gas at room temperature (exothermic reaction.). After 30 min of the addition of HCl gas, the reaction mixture was covered with a cap and stirred at room temperature for 16 hrs. The solvent was then carefully removed by evaporation, the resulted residue was treated with saturated NAHC03 solution, and the precipitate was collected by filtration. After drying on the vacuum pump for overnight, the crude material, 2-fluoro-4-nitro-benzoic acid methyl ester was directly used for the next step without further purification. LC/Method A/2.64 min.5 ml of concentrated sulfuric acid was added to a methanol (1300 ml) solution of 140 g of 2-fluoro-4-nitrobenzoic acid, and heated under reflux for 48 hours. The solvent was evaporated away under reduced pressure, water was added to the residue, and the formed solid was taken out through filtration. This was dried under reduced pressure to obtain 141 mg of the entitled compound as a yellow solid.Reference (Step 1) Production of methyl 2-fluoro-4-nitrobenzoate: Concentrated sulfuric acid (5 ml) was added to a methanol (1300 ml) solution of 2-fluoro-4-nitrobenzoic acid (140 g), and heated under reflux for 48 hours. The solvent was evaporated away under reduced pressure, water was added to it, and the formed solid was taken out through filtration. After dried under reduced pressure, the entitled compound was obtained as a yellow solid.471a) Synthesis of Methyl 2-Fluoro-4-nitrobenzoate.To a 500ml round bottom flask, 2-fluoro-4-nitrobenzoic acid (1 1.68g, 63.1mmoles), toluene (200ml) and methanol (30ml) were added, respectively. Trimethylsillyldiazomethane (2M) in diethyl ether (38ml, 76mmoles) was then added dropwise at romm temperature over 30 minutes. The solution was then stired for lhour. The sovents were then removed under vaccum to afford a yellow solid. The residual solvent was co-evaporated with methanol (100ml) to give 12.52g of yellow solid (100% yield). NMR lH-(DMSO)-I'-8.28 (d, IH, J=7.58Hz), 8.10-8.22 (m, 2H), 3.93 (s, 3H).

Molecular Weight:199.14
XLogP3:1.6
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:199.02808583
Monoisotopic Mass:199.02808583
Topological Polar Surface Area:72.1
Heavy Atom Count:14
Complexity:240
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes