3-AMINO-5-NITROBENZOIC ACID METHYL ESTER

b. Methyl-5-amino-3-nitrobenzoate.; 5-Amino-3-nitrobenzoic acid (18.5 g, 0.10 mol) was esterified in methanol (160 ml) by bubbling dry hydrogen chloride into the solution. After saturation, the mixture was stirred over night at ambient temperature. The mixture was then evaporated to a crystalline residue. This was taken up in methylene chloride and washed with diluted sodium hydrogen carbonate solution (5 percent) until pH 7-8 in aqueous phase. The organic phase was separated, dried (MgSO3-amino-5-nitro-benzoic acid (25 g; 0.14 mol) in 250 ml methanolic hydrogen chloride solution was heated at70 C for 3 hours. The mixture was concentrated in vacuo, diluted in ethyl acetate, washed with NaHCO3 solution andthe organic phase concentrated. 25 g (0.13 mmol; 91percent yield) of 3-amino-5-nitro-benzoic acid methyl ester were obtained, as a yellow solid.To a solution of 3-amino-5-nitro-benzoic acid (65 g, 357 mmol, 1 equiv) in MEOH (650 ml) at 0 C was added SOCI2 dropwise (39 ml, 536 mmol, 1.5 equiv). The resulting solution was allowed to warm to room temperature and stirred for 16 h. A further portion of SOCI2 (10 ml, 137 mmol, 0.4 equiv) was added dropwise and the solution was stirred at room temperature for 5 h, at 50 C for 2 h and then cooled to room temperature and concentrated in vacuo. The residue was dissolved in AcOEt and the organic phase washed with saturated aqueous NAHC03 solution, dried over MGS04 and concentrated in vacuo. The solid residue was triturated with ACOET/ISO-HEXANE to give 3-amino-5-nitro-benzoic acid methyl ester (D1) (55 g, 78percent) as a pale yellow solid.To a solution of 3-amino-5-nitro-benzoic acid (ex Avocado) (65 g, 357 [MMOL, ] 1 equiv) in MeOH (650 ml) at 0 C was added [SOC12] dropwise (39 ml, 536 mmol, 1.5 equiv). The resulting solution was allowed to warm to room temperature and stirred for 16 h. A further portion of [SOC12] (10 [ML, ] 137 mmol, 0.4 equiv) was added dropwise and the solution was stirred at room temperature for 5 h, at 50 C for 2 h and then cooled to room temperature and concentrated in vacuo. The residue was dissolved in EtOAc and the organic phase washed with saturated NaHCO3 solution, dried over [MGSO4] and concentrated in vacuo. The solid residue was triturated with EtOAc/iso-hexane to give the title compound (55 g, 78percent).Iron based nanomaterial (12.4 mg, 3.6percent) was placed into an oven dried 4 mL microwave reaction vial containing a PTFE-coated magnetic stir bar. The reaction vial was closed with a rubber septum and 0.5 mL aqueous solution of 2 wtpercent TPGS-750-M was added via syringe. The mixture was stirred at RT for 1 mm. The septum was removed and NaBH4 (21 mg, 0.55 mmol) was slowly added to the mixture. (Caution- NaBH4 should be added very slowly, especially for large scale reactions). During addition of NaB H4, the reaction turned black with evolution of hydrogen gas. 3, 5-Dinitrobenzoic acid (106 mg, 0.5 mmol, dispersed in 0.5 mL aqueous TPGS-750-M in advance) was added to the catalyst suspension via canula. The reaction vial was filled with argon and covered, and stirred at rt for 1 h, and monitored by TLC. After complete consumption of starting material (TLC), and the mixture was extracted with EtOAc (1 mL x 3), the combined organic extracts were concentrated under vacuum to obtain a yellowish solid (contains 5percent over-reduced product). The resulting solid was placed into another oven dried 4 mL microwave reaction vial containing methanol (1 mL), EDC (114 mg, 0.6 mmol), and DMAP (1 mg, 0.01 mmol). The mixture was stirred at ft for 6 h. After reaction completion, the mixture was washed with dilute HC1 (1 M, 1 mL x 3), saturated NaHCO3 and then brine. The combined organic extracts were dried over anhydrous Na2SO4. Volatiles were removed under reduced pressure to obtain crude product that was purified by flash chromatography over silica gel with EtOAc/hexanes (15/85) to obtain pure 3-amino-5-nitrobenzoate (88 mg, 0.42 mmol, 84percent). ‘H NMR (500 MHz, CDC13) 8.20 (s, 1H), 7.66 (s, 1H), 7.62 (s, 1H), 3.95 (s, 3H); ‘3C NMR (126 MHz, CDC13) 165.28, 149.28, 147.32, 132.43, 121.21, 114.25, 112.83, 52.66; GC-MS, mlz: 196 [Mj.The solution of (NH

Molecular Weight:196.16
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:196.04840674
Monoisotopic Mass:196.04840674
Topological Polar Surface Area:98.1
Heavy Atom Count:14
Complexity:238
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes