Methyl 2-bromo-4-methylbenzoate

off-white powder

Concentrated sulfuric acid (4 mL) was added to a solution of 2-Bromo-4- methyl benzoic acid (10.0 g, 46.5 mmol) in dry methanol (200 ml). The reaction mixture was heated to reflux for 18h. After cooling, the reaction mix was concentrated and the residual was partitioned between water and ethyl acetate. The layers were separated and the aqueous was extracted with EtOAc (3 x 100 ml). The combined organic extracts were washed with saturated NaHCOCompound 89.1. Methyl 2-bromo-4-methylbenzoate. A solution of 2-bromo-4- methylbenzoic acid (10.0 g, 46.5 mmol) in MeOH (50 mL) was cooled to 0 °C, then concentrated sulfuric acid (10 mL) was carefully added. The mixture was heated at 70 °C for 2 hours. After cooling to room temperature, the volatile organics were removed under reduced pressure, and the residue was poured onto ice-water (100 mL). The mixture was extracted with EtOAc (x2) and the combined organic extracts were washed with aq. NaHC0Compound 89.1. Methyl 2-bromo-4-methylbenzoate. A solution of 2-bromo-4- methylbenzoic acid (10.0 g, 46.5 mmol) in MeOH (50 mL) was cooled to 0 °C, then concentrated sulfuric acid (10 mL) was carefully added. The mixture was heated at 70 °C for 2 hours. After cooling to room temperature, the volatile organics were removed under reduced pressure, and the residue was poured onto ice-water (100 mL). The mixture was extracted with EtOAc (x2) and the combined organic extracts were washed with aq. NaHC0Step 1: To a solution of 2-bromo-4-methyl-benzoic acid (5.50 g, 25.6 mmol) in methanol (250 mL) was added concentrated sulfuric acid (1 mL). The reaction mixture was heated to reflux overnight (approximately 16 hours), allowed to cool to room temperature and then concentrated to approximately {fraction (1/4)} volume under reduced pressure. The residue was then partitioned between water and ethyl acetate, the layers were separated and the aqueous layer was extracted with one additional portion of ethyl acetate. The combined organics were washed one time with saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered through a plug of silica gel and concentrated under reduced pressure. 2-Bromo-4-methyl-benzoic acid methyl ester was obtained as an oil (4.95 g, 85percent). To a solution of this oil (2.50 g, 10.9 mmol) in carbon tetrachloride (100 mL) was added N-bromosuccinimide (2.04 g, 11.5 mmol) and benzoylperoxide (0.106 g, 0.44 mmol). The reaction mix was heated to reflux. After approximately 1 hour, the reaction mixture became colorless. At this time the heat was removed to allow the mixture to cool to room temperature and the mixture was filtered. The filtrate was concentrated under reduced pressure. The crude mixture was purified by HPLC (40percent methylene chloride in hexane) to give 2-bromo-4-bromomethyl-benzoic acid methyl ester (1.50 g, 45percent) as a white powder. (1) To a solution of the Compound 1 (15 g) in methanol (200 mE) was added dropwise thionyl chloride (10.2 mE) under ice-cooling, and the resulting mixture was stirred at the same temperature for 1 hout Thionyl chloride (10.2 mE) was added thereto, and the resulting mixture was stirred at 40° C. for 15 minutes, stirred at 45° C. for 45 minutes, and then stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, and then a saturated aqueous solution of sodium hydrogen carbonate and chloroform were added thereto, and the resulting mixture was stirred, and then extracted with chloroform. The resulting organic layers were dried, and then concentrated under reduced pressure to give the Compound 2 (17.84 g) as a pale yellow viscous material. MS (APCI): m/z 229/231 [M+H]2-Bromo-4-methyl-benzoic Acid Methyl Ester (55B): Step 1: A solution of 67 A (50 mg, 0.103 mmol) in DMF (2 mL) was treated with

Molecular Weight:229.07
XLogP3:2.8
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:227.97859
Monoisotopic Mass:227.97859
Topological Polar Surface Area:26.3
Heavy Atom Count:12
Complexity:170
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes