5-BROMO-2-BROMOMETHYL-BENZOIC ACID METHYL ESTER

A mixture of methyl 5-bromo-2-methylbenzoate (1 g, 4.4 mmol), N- bromosuccinimide (0.80 g, 4.4 mmol), benzoyl peroxide (56 mg, 0.23 mmol) in carbon tetrachloride (20 mL) was stirred at 85 °C for 2 hours. The mixture was filtered through a pad of silica gel and concentrated in vacuo to afford the desired product (1.3 g, 97percent yield). ESI-MS m/z: 306.0 [M+H]A mixture of 5-bromo-2-methyl-benzoic acid methyl ester (500 mg, 2.19 mmol), N- bromosuccinimide (389 mg, 2.18 mmol) and AIBN (18 mg, 0.11 mmol) in CC1(2) The compound (200 g, 0.87 mol) obtained in step (1) was dissolved in 2 liters of carbon tetrachloride.NBS (154 g, 0.87 mol) and benzoyl peroxide (25 g, 0.087 mol) were added.The system was heated at reflux for 6 hours, then cooled and filtered. The filter cake was washed with carbon tetrachloride. The organic phase is concentrated, The residue is dissolved in a 1:4 mixture of ethyl acetate and petroleum ether and then filtered.228 g of brominated product was obtained in a yield of 85percent.To a solution of 5-Brorno-2-methyl-benzoic acid methyl ester (1 equiv) in chloroform (0.1 M) were added N-bromosuccinimide (1.2 equiv) and benzoyl peroxide (0.05 equiv). The reaction mixture was stirred at reflux for 16 hours. It was then diluted with chloroform and a precipitate was collected by vacuum filtration on a sintered funnel. The filtrate was concentrated in vacuo. The subsequent residue was purified by flash column chromatography To a solution of 5-bromo-2-methylbenzoic acid methyl ester (8.4 g, 37 mmol) in 100 mL CClA) methyl 5-bromo-2- (bromomethyl ) benzoate To a solution of methyl 5-bromo-2-methylbenzoate (5.27 g) in trifluoromethylbenzene (50.0 mL) were added AIBN (0.04 g) and N-bromosuccinimide (4.50 g) , and the mixture was stirred at 90°C for 4 hr under argon atmosphere. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with saturated brine. The organic layer was dried over, anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (4.89 g). A mixture of methyl 5-bromo-2-methylbenzoate (3.5 g), N-bromosuccinimide (3.0 g), 2, 2′-azobis(isobutyronitrile) (0.251 g) and (trifluoromethyl)benzene (40 mL) was stirred under nitrogen atmosphere at 80° C. for 5 hr. The reaction mixture was diluted with a mixture of ethyl acetate-hexane, purified by silica gel column chromatography (hexane/ethyl acetate), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (3.88 g). (1077) A) Place 5-bromo-2-methyl-benzoic acid (1.0 g, 4.7 mmol) in a 200 mL flask under an N2 atmosphere and add methanol via syringe. Add a 2M solution of diazomethyl- trimethyl-silane in hexane (3.5 mL, 23.0 mmol) drop wise over 10 minutes and stir for 1 hour at room temperature. Add glacial acetic acid (16 mL) and stir for 45 minutes. Dilute with ethyl acetate (100 mL) and wash with 1M aqueous sodium hydroxide solution (30 mL), saturated aqueous sodium bicarbonate solution (30 mL) and brine (30 mL). Dry the organic layer (Na2SO4), filter and concentrate in vacuo to obtain 1.01 g of 5-bromo-2- methyl-benzoic acid methyl ester (99 percent). Place 5-bromo-2-methyl-benzoic acid methyl ester (1.04 g, 4.5 mmol) in a 50 mL flask under a N2 atmosphere and add carbon tetrachloride (15 mL). Add N-bromo- succinamide (1.49 g, 8.3 mmol) and 2, 2'-azobisisobutyronitrile (40 mg, 0.2 mmol) and fit flask with a condenser and reflux for 4 hours. Cool to room temperature and filter. Concentrate the filtrate and pre-adsorb the crude product onto silica gel. Chromatograph the residue on a Si02 column eluting with dichloromethane in hexane (0 to 50percent) to obtain 977 mg of 5-bromo-2-bromomethyl-benzoic acid methyl ester (70percent). Using 5-bromo-2-bromomethyl-benzoic acid methyl ester (0. 984 g, 3.20 mmol) and the procedure described in the I st paragraph for the alternative procedure for 5- (4, 4, 5, 5-tetramethyl- [1, 3, 2] dioxaborolan-2-yl) -2, 3-dihydro-isoindol-1-one, prepare 509 mg of the title compound (75 percent).

Molecular Weight:307.97
XLogP3:3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:307.88706
Monoisotopic Mass:305.88910
Topological Polar Surface Area:26.3
Heavy Atom Count:13
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes