2-BROMOMETHYL-4-NITRO-BENZOIC ACID METHYL ESTER

U) 2-Bromomethyl-4-nitro-benzoic acid methyl esterN-Bromosuccinimide (2.18 g, 12.30 mmol) was added to a stirred solution of 2- methyl-4-nitro-benzoic acid methyl ester (2 g, 10.25 mmol) and ABCN (626 mg, 2.56 mmol) in carbon tetra-chloride (80 ml) at room temperature. The reaction was heated at reflux for 2 hrs and then allowed to cool to room temperature and stirred for 15 hrs. The solvent was evaporated in vacuo and the resulting residue filtered through a pad of silica (eluting with dichloromethane). The solvent was evaporated in vacuo to afford the title compound as a yellow solid (2.70 g, 96percent). HPLC retention time 4.49min. Mass spectrum (ES+) m/z 256 (M+H).EXAMPLE 76In a 500 mL, 3-neck round-bottomed flask, the intermediate (1) (20 g, 88.01 mmol) was charged with CC1To a solution of 2-methyl-4-nitrobenzoic acid methyl ester (2.0 g, 10.36 mmol) in carbon tetrachloride (80 mL) and l , azobis(cyclohexanecarbonitrile) (0.63 g, 2.56 mmol) was added N-bromosuccinimide (2.18 g, 12.25 mmol) and the resulting solution was heated at reflux for 5h and allowed to sit at room temperature overnight. The reaction was concentrated under reduced pressure and to the resulting residue was added DCM. The solid was filtered off and washed several times with DCM. The combined filtrate and washes were loaded onto a silica column and eluted with 10percent EtOAc/hexane to provide slightly impure methyl 2-(bromomethyl)-4-nitrobenzoate (1.82 g, 65percent yield) which was carried on as is to the next step.A solution of Intermediate 58 (9.57 g, 49 mmol), NBS (9.6g, 54 mmol), benzoyl peroxide (121 mg, 0.5 mmol) in carbon tetrachloride was heated at 85°C for 18 h. The reaction was concentrated under vaccum, analysed by TLC and A solution of 19 (2.57 g, 13.19 mmol) in 1, 2-dichloroethane (100 mL) was treated with N-bromosuccinimide (2.3 g, 13.19 mmol) and benzoyl peroxide (0.26 g), and the mixture was kept at reflux for 2 days, then cooled, washed with water, and evaporated to a yellow oil (3.52 g). The oil was dissolved in acetone and silica gel (4.0 g) was added. A dry silica gel plug was obtained after evaporation of the solvent. The plug was loaded on to a silica gel column and eluted with 10percent ethyl acetate in hexane to afford 20 (1.73 g, 48.2percent) as a yellow oil; R2 - methyl-4-nitrobenzoate (. 200mg, 1 OmmoL), benzoyl peroxide (48.5mg, 0.2mmoL), N_-bromosuccinimide (213mg, 1.2mmoL) was added to the CCl4 (15mL), and under protection of Ar gas, the reaction was heated at reflux for 7 hours, cooled, washed with saturated sodium bicarbonate (3 X20mL ), saturated brine (20 mL), dried and the solvent was distilled off under reduced pressure, the residue was purified by flash column chromatography, eluent PE: ΕΑ = 20: 1, to give a white solid 124mg, 44percent yieldAzobisisobutyronitrile (AIBN) (0.17 g, 1.02 mmol) was added to the solution of methyl 2-methyl-4-nitrobenzoate (61.2) (2.0 g, 10.2 mmol) and N-bromosuccinimide (NBS) (2.7 g, 15.2 mmol) in CCl2-Methyl-4-nitro - benzoic acid methyl ester (3.0 g, 15 mmol) wasdissolved in carbon tetrachloride (50 mL), and then were added N- bromosuccinimide (3.0 g, 17 mmol) and benzoyl peroxide (100mg, 0.4 mmol), the addition was complete the reaction was refluxed for 10hours. Completion of the reaction, the reaction solution was cooled toroom temperature, filtered, and the filtrate was washed with saturated sodiumbicarbonate solution and water, dried over anhydrous sodium sulfate, filteredand concentrated. Was purified by silica gel column chromatography usingconcentrated to give the intermediate 2-bromomethyl-4-nitro - benzoic acidmethyl ester (pale yellow solid, 1.9 g).

Molecular Weight:274.07
XLogP3:2.2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:272.96367
Monoisotopic Mass:272.96367
Topological Polar Surface Area:72.1
Heavy Atom Count:15
Complexity:253
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes