4-Bromo-3,5-dimethoxybenzyl alcohol

A solution of LiAlHTo an oven dried round bottom flask was added 4-bromo-3, 5-dimethoxybenzoic acid (Compound 8, 2 g, 7.66 mmol) and anhydrous tetrahydrofuran (24 mL). Borane dimethylsulfide complex (7.6 mL of 2M in tetrahydrofuran, 15.3 mmol) was added drop-wise at room temperature. The reaction was heated overnight at 40 °C. The reaction was quenched using hydrochloric acid (IN) and partitioned between ethyl acetate and water. The organic layer was washed using brine, dried with sodium sulfate, filtered and concentrated in vacuo. (0421) Product, (4-bromo-3, 5-dimethoxyphenyl)methanol, (compound 10, 1.89 g, quantitative yield) was isolated as a white solid. LC-MS: tR=1.748 min; m/z=229.0, 231.0 (dehydration). 4-bromo-3, 5-dimethoxy - benzoic acid (4.0 g, 15 mmol) was dissolved in tetrahydrofuran (50 mL), borane-tetrahydrofuran complex 1 M tetrahydrofuran solution (23 mL, 23mmol) were added at 0 , heating under reflux for 1 hour and the mixture was stirred. The reaction was quenched with water at 0 , and concentrated under reduced pressure. The resulting residue water, Soshi ethyl acetate added thereto to and the organic phase was washed with saturated aqueous sodium chloride solution. The organic phase to give the title compound (3.0 g) by drying under reduced pressure and concentrated over anhydrous sodium sulfate.To a microwave vial was added 4-bromo-3, 5-dimethoxybenzyl methane sulfonate (36, 3.68 g, 1 1.3 mmol) and ethanol (20 mL). Potassium carbonate (2.34 g, 16.9 mmol) was added followed by potassium iodide (catalytic) and the reaction was irradiated with microwaves at 140 °C for 2 hours. The reaction was filtered through a plug of Celite® and rinsed with additional ethanol. The solvent was removed in vacuo and the resulting oil was purified on silica gel using ethyl acetate and hexanes as eluent. Product 2-bromo-5-(ethoxymethyl)-l, 3-dimethoxybenzene (37, 1.77 g, 57percent yield) was isolated as an oil. LC: t(4-Bromo-3, 5-dimethoxyphenyl)methanol (2.11 g) was dissolved in tetrahydrofuran (8.3 mL), and subsequently 3, 4-dihydro-2H-pyran (1.56 mL) and p-toluenesulfonic acid monohydrate (0.16 g) were added thereto. The mixture was stirred for 13.3 hours at room temperature under a nitrogen atmosphere. Tetrahydrofuran (5 mL) was added thereto, and then a 2.77 M n-butyllithium-hexane solution (3.3 mL) was added dropwise thereto at an internal temperature of -76.7 to -61.3°C. Three minutes after the dropwise addition, 5 mL of tetrahydrofuran was further added, and the mixture was stirred for 53 minutes in a dry ice-acetone bath. Triisopropyl borate (2.4 mL) was added dropwise thereto at an internal temperature of -76.4 to -68.7°C, and the mixture was stirred for 30 minutes at the same temperature, and then stirred for one hour at room temperature. 10 mL of 1 N hydrochloric acid was added thereto, and the mixture was stirred for 2.5 hours at room temperature. 5 N hydrochloric acid (6 mL) was added thereto, and the mixture was stirred for 2. 7 hours at the same temperature. The reaction system was left to stand still, and the lower layer was obtained by partition. A 2 N aqueous solution of sodium hydroxide was added to the lower layer to adjust to pH 7 to 8. The upper layer was extracted two times with a 2 N aqueous solution of sodium hydroxide (5 mL each), and the extracts were combined with this liquid. The obtained alkaline extracted layer was washed with t-butyl methyl ether (20 mL), and then was adjusted to pH = 2 to 3 with 5 N hydrochloric acid. The extracted layer was subjected to extraction four times with ethyl acetate (20 mL each). The combined ethyl acetate extracted layer was washed with 10 mL of saturated brine, and was dried over anhydrous magnesium sulfate. The residue was dried under reduced pressure at 45°C, and was dried in a vacuum at room temperature, to obtain 909 mg (yield 50.2percent) of the target product. 1H-NMR (CDCl3): delta: 3.92 (s, 6H), 4.73 (s, 2H), 6. 61 (dd, J= 6.8, 1.2 Hz, 1H), 6.65 (s, 2H), 7.19 (s, 2H).

Molecular Weight:247.09
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:245.98916
Monoisotopic Mass:245.98916
Topological Polar Surface Area:38.7
Heavy Atom Count:13
Complexity:140
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes