2-Bromo-1,3-dimethoxybenzene

off-white crystalline solid

Production Example (A) Synthesis of Intermediate (A) [Show Image] (A-1) Synthesis of 1-bromo-2, 6-dimethoxybenzene In the atmosphere of argon, 19.3g of 1, 3-dimethoxybenzene and 500 mL of anhydrous diethyl ether were placed in a flask. 105 mL (1.6M) of a hexane solution of n-butyllithium was added, and the resulting reaction solution was stirred with heating for 4 hours. After cooling to room temperature while stirring, the reaction solution was cooled to -50°C, followed by dropwise addition of 25g of bromine. Then, while heating the reaction solution to room temperature, stirring was conducted for 2 hours. Then, 300 mL of an aqueous 10percent sodium thiosulfate solution was added, and the resulting mixture was stirred for 1 hour. The reaction solution was extracted with ether, and an aqueous phase was removed, and then, an organic phase was washed with saturated saline. The organic phase was dried with magnesium sulfate and concentrated. Residues were purified by means of silica gel column chromatography. The resulting crystals were washed with hexane, whereby 17.9g (yield: 52percent) of white crystals of 1-bromo-2, 6-dimethoxybenzene were obtained.Under an argon atmosphere 1, 3-dimethoxy benzene (19.3g), was charged with anhydrous diethyl ether (500mL) to the flask, added 1.6M n-butyl lithium in hexane solution (105mL), the reaction solution was stirred for 4 hours under heating. After cooling to room temperature with continuous stirring, cooled to -50 ° C., was added dropwise bromine (25 g). The reaction solution was stirred for 2 hours while warming to room temperature. 10percent aqueous solution of sodium thiosulfate (300mL) added, and the mixture was stirred for 1 hour. The reaction solution was extracted with ether, after removing the aqueous layer, the organic layer was washed with saturated brine. The organic layer was dried over magnesium sulfate, concentrated, and the residue was purified by silica gel chromatography. The obtained crystals were washed with hexane to obtain Intermediate 14 (17.9g). The yield was 52percent.General procedure: A mixture of carboxylic acid (1 equiv., 0.5 mmol), CuBr2 or CuCl2 (2 equiv., 1 mmol), Ag2CO3 (1 equiv., 0.5 mmol) and PdCl2 (0.1 equiv.) was heated inTHF (3 mL) under reflux at 110 oC for 24 h. After the reaction finished, the mixture was evaporated under vacuum and purified by columnchromatography to afford the desired product.REFERENCE EXAMPLE 3(1)

Molecular Weight:217.06
XLogP3:2.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:215.97859
Monoisotopic Mass:215.97859
Topological Polar Surface Area:18.5
Heavy Atom Count:11
Complexity:107
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes