Methyl 5-bromo-2-methyl-3-nitrobenzoate

Preparation of methyl 5-bromo-2-methyl-3-nitrobenzoate (‘2-2, A mixture of 5.bromo-2-methyl-3-nitrobenzoic acid (‘2-1(21.2 g, 81.5 mmol) in SOC12 (100 mL) washeated to retlux until the mixture became clear (about 1.5 hrs). The reaction mixture was cooled and concentrated in vacuo, The residue was added portionwise to 250 mL of MeOH. The resulting mixture was stirred overnight under refluxing. The reaction mixture was cooled and concentrated. The residue was dissolved in 300 mL of hA, washed sequentially with sat. aq. NaHCO3 and brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (silica gel, PE:EA (20:1, v:v)) to yield compound C2-2 as a light yellow solid (21.2 g, yield: 95percent).To a solution of 5-bromo-2-methyl-3-nitro-benzoic acid (1 g, 3.85 mmol, 1 equivalent) in MeOH (20 mL) was added HA mixture of 5-bromo-2-methyl-3-nitrobenzoic acid (12 g, 41 mmol) in SOClA mixture of 5-bromo-2-methyl-3-nitrobenzoic acid (12 g, 41 mmol) in 50C12/MeOH(v:v=1:10) (250 mE) was heated to reflux overnight. The reaction mixture was cooled and concentrated. The residue was dissolved in 300 mE of EA. The organic layer was washed sequentially with sat. aq. NaHCO3 and brine, dried over Na2504, and concentrated. The residue was purified by chromatography (silica gel, PE:EA (20:1, v:v)) to afford Methyl 5-bromo-2- methyl-3-nitrobenzoate (11 g, yield: 87percent). 1H NMR: (400 MHz, CDC13): ö 8.12 (d, J=2.0 Hz, 1H), 7.97(d, J=2.0 Hz, 1H), 3.95(s, 3H), 2.57(s, 3H). Chemical Formula: C9H813rN04; Molecular Weight: 272.96. Total H count from ‘HNMR data: 8.To a stirred solution of 5-bromo-2-methyl-3-nitrobenzoic acid (7.28 g, 28.0 mmol) in DMF (100 mL) was added sodium carbonate (11.9 g, 112 mmol) and methyl iodide (15.9 g, 112 mmol). The reaction mixture was stirred at 60° C. for 8 hours. After completion of the reaction, the reaction mixture was filtered and washed with ethyl acetate. The combined filtrate was washed with water and the aqueous phase was re-extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the titled compound as a solid. (7.74 g, quantitative yield). [0998] Step 2: methyl 5-bromo-2-meth -3-nitrobenzene[0999] To a stirred solution of 5-bromo-2-methyl-3-nitrobenzoic acid (287 g, 1 103 mmol) in DMF (1 50 mL), sodium carbonate (468 g, 4415 mmol) and methyl iodide (626.63 g, 4415 mmol) were added. Resulting reaction mass was heated at 60 °C for 8 h. On completion, solid precipitated was filtered, residue washed with diethyl ether (5 times). Combined organic layers were dried, concentrated under reduced pressure giving the desired compound (302 g, 99percent) which was used for further reaction.To a stirred solution of 5-bromo-2-methyl-3-nitrobenzoic acid (29 g, 111.9 mmol) in DMF (300 mL), sodium carbonate (48 g, 447.8 mmol) and Mel (63.59 g, 447.8 mmol) were added. The resulting reaction mass was heated at 60 °C for 12 h.The progress of the reaction was monitored by TLC. Upon completion, the reaction mixture was filtered and washed with diethyl ether. The filtrate was diluted with water and extracted with diethyl ether. The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure. The crude compound was purified by column chromatography to afford the title compound (30 g, 98percent)Methyl 5-bromo-2-methyl-3-nitrobenzoate To a stirred solution of 5-bromo-2- methyl-3-nitrobenzoic acid (285 g, 1105 mmol) in DMF (2.8L) at room temperature was added sodium carbonate (468 g, 4415 mmol) followed by addition of methyl iodide (626.6 g, 4415 mmol). The resulting reaction mixture was heated at 60 °C for 8 h. After completion (monitored by TLC), the reaction mixture was filtered (to remove sodium carbonate) and washed with ethyl acetate (1L X 3). The combined filtrate was washed with water (3L X 5) and the aqueous phase was back extracted with ethyl acetate (1L X 3). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the title compound as a solid (290g, 97percent yield). The isolated compound was taken directly into the next step. 1H NMR (CDC1[0325] Step 2: Synthesis of methyl -bromo-2-methyl-3-nitrobenzoate [0326] To a stirred solution of 5-bromo-2-methyl-3-nitrobenzoic acid (285 g, 1105 mmol) in DMF (2.8L) at room temperature was added sodium carbonate (468 g, 4415 mmol) followed by addition of methyl iodide (626.6 g, 4415 mmol). The resulting reaction mixture was heated at 60 °C for 8 h. After completion (monitored by TLC), the reaction mixture was filtered (to remove sodium carbonate) and washed with ethyl acetate (1L X 3). The combined filtrate was washed with water (3L X 5) and the aqueous phase was back extracted with ethyl acetate (1L X 3). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the title compound as a solid (290g, 97percent yield). The isolated compound was taken directly into the next step. 1H NMR (CDC1Methyl 5-bromo-2-methyl-3-nitrobenzoateTo a solution of 5-bromo-2-methyl-3-nitrobenzoic acid (10 g, 38.5 mmol) in DMF (100 mL) were added sodium carbonate (16.30 g, 154 mmol) and methyl iodide (9.62 mL, 154 mmol) at room temperature and the reaction mixture was stirred at 55 °C for 10 hours. On completion, the reaction mixture was filtered and the inorganic solid residue was washed with ethyl acetate. The filtrate was concentrated under vacuum till dry and re- dissolved in ethyl acetate before washing with 5 percent sodium bicarbonate solution (70 mL) followed by 5.0 M HC1 solution (30 mL). The organic layer was finally washed with brine, dried over sodium sulfate and concentrated to yield 10 g (95percent) of the title compound. [01038] Step 3: methyl 5-bromo-2-methyl-3-nitrobenzoate [01039] To a stirred solution of 5-bromo-2-methyl-3-nitrobenzoic acid (16 g, 61.5 mmol) in DMF (160 mL), was added iodomethane (35.7 g, 248 mmol) and sodium carbonate (26.3 g, 248 mmol). The resulting reaction mixture was stirred at 60 °C for 8h. On completion, the reaction mixture was filtered and the inorganic solid residue washed with ethyl acetate. The combined filtrates were concentrated under vacuum till dry and re-dissolved in ethyl acetate before washing with 5percent sodium bicarbonate solution (700 mL) followed by 5M HC1 solution (300 mL). The organic layer was finally washed with brine, dried over sodium sulfate and concentrated to afford pure methyl 5-bromo-2-methyl-3-nitrobenzoate (16 g, 94.5percent).The 2-methyl-3-nitro-5-bromobenzoic acid (16g, 61.5mmol) dissolved in DMF (160 ml) solution, then to add iodomethane (35.7g, 248mmol) and sodium carbonate (26.3g, 248mmol). Reaction solution 60 °C stirring 8h. After, when the reaction is complete, the reaction system filter in order to remove the inorganic salt, filtered salt of washing with ethyl acetate. After combining the filtrate in vacuo, diluted by adding acetic acid ethyl ester, using 5percent sodium bicarbonate aqueous solution (700 ml) washing, then using 5M hydrochloric acid solution (300 ml) washing. The organic phase after washing of salt water, drying with anhydrous sodium sulfate, vacuum concentration to obtain 5-bromo-2-methyl-3-nitro-benzoic acid methyl ester 16g, the yield is 94percent.To a mixture of methyl 5-bromo-2-methyl-3-nitrobenzoic acid (5 g, 19.2 mmol) and iodomethane (4.79 ml. and 76.9 mmol) in DMF (70 ml.) was added sodium carbonate (6.46 g, 76.9 mmol). The reaction mixture was stirred at 6OTo a solution of methyl 5-bromo-2-methylbenzoate (19.1 g, 83.41 mmol) in concentrated H

Molecular Weight:274.07
XLogP3:2.7
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:272.96367
Monoisotopic Mass:272.96367
Topological Polar Surface Area:72.1
Heavy Atom Count:15
Complexity:265
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes