METHYL5-METHOXY-2-NITROBENZOATE

A pressure flask was charged with 2-nitro-4-methoxybenzoic acid (3.98 g, 0.020 mol) and methanol(10 mL). Concentrated H2SO4 (150 μl) was added dropwise. The flask was sealed and stirred at85 °C for 4 days. The mixture was cooled and concentrated to approximately half of its originalvolume. Ethyl acetate (25 mL) was added, and the mixture was washed with water (25 mL), saturated aqueous NaHCO3 solution (2 × 25 mL), brine (2 × 25 mL) and water (2 × 25 mL). Theorganic layer was dried over MgSO4, filtered, and concentrated in vacuo to give the title compoundas a yellow oil (3.57 g, 87percent); 1H NMR (300 MHz, CDCl3) δ 8.04 (d, J = 8.8 Hz, 1H, H6), 7.04 (d, J = 2.3 Hz, 1H, H3), 7.00 (dd, J = 8.8, 2.8 Hz, 1H, H4), 3.93 (s, 3H, OMe), 3.91 (s, 3H, OMe);13C {1H} NMR (75 MHz, CDCl3) δ 166.7, 163.5, 140.2, 131.4, 126.8, 115.9, 114.2, 56.4, 53.5; datain accordance with literature values.5Fuming hydrochloric acid was passed through an ice-cooled solution of 5-methoxy-2-nitrobenzoic acid (10g, 50.7mmol) in methanol (70mL) until saturated. The reaction mixture was warmed to room temperature for 18 hours and was then heated under reflux for 4 hours. The solvent was then evaporated under reduced pressure and the residue was partitioned between ethyl acetate and sodium hydrogen carbonate solution. The organic layer was separated and washed with sodium hydrogen carbonate solution and brine, dried over magnesium sulfate, and concentrated in vacuo to give the title compound as a brown oil in 77percent yield, 8.23g. 5-Methoxy-2-nitro-benzoic acid (3.2 g) was dissolved in N, N-dimethylformamide (60 ml). Potassium carbonate (5.61 g) and methyl iodide (5.05 ml) were added to the solution, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the organic layer was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography with an acetone-hexane system to give methyl 5-methoxy-2-nitro-benzoate (3.38 g, yield 99percent). Methyl 5-methoxy-2-nitro-benzoate (3.38 g) was dissolved in N, N-dimethylformamide (34 ml). Triethylamine(7 ml) and 20percent palladium hydroxide (340 mg) were added to the solution, and the mixture was stirred under a hydrogen gas atmosphere at room temperature overnight. The reaction mixture was filtered and was washed with chloroform. The solvent was removed by distillation under the reduced pressure, water was added to the residue, and the organic layer was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine, was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography with an acetone-hexane system to give methyl 2-amino-5-methoxy-benzoate (2.87 g, yield 99percent).Methyl 5-hydroxy-2-nitrobenzoate (26.45 g, 0.134 mol) was dissolved in DMF in a 1000 ml one-Methyl iodide (20.95 g, 0.148 mol) andK2CO3 (37.08 g, 0.268 mol), Reaction at room temperature 3h.The reaction was completed, the reaction solutionPour into the water that is solid precipitation, suction filtration, The filter cake was collected to obtain 28.05 g of methyl 2-nitro-5- (methoxy) benzoate in a yield of 99percent.5-methoxy-2-nitrobenzoic acid (2 g, 10.14 mmol) was dissolved in MeOH (50.7mL). 50C12 (2.96 mL, 40.6 mmol) was added and the reaction mixture was heated to reflux for 20 hours. The reaction mixture was concentrated in vacuo. The cmde material was dissolved in EtOAc and washed with 1 N NaOH, then water, then brine, dried (Na2504), filtered, and concentrated in vacuo to give Intermediate 159A (1.7786 g, 8.42 mmol, 83percent) as a brown oil: ‘H NMR (400MHz, CHLOROFORM-d) 8.04 (d, J=9.0 Hz, 1H), 7.07-6.99 (m, 2H), 3.94 (s, 3H), 3.92 (s, 3H); LC-MS: Method H, The compound did not ionize.

Molecular Weight:211.17
XLogP3:1.7
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:211.04807239
Monoisotopic Mass:211.04807239
Topological Polar Surface Area:81.4
Heavy Atom Count:15
Complexity:249
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes