5-BROMO-2-(HYDROXYMETHYL)PHENOL

To a suspension of LAH (2.27 g, 60 mmol) in EtBorane-dimethylsulphide complex (1.1 mL, 11.58 mmol) was added dropwise to a solution of 4-bromo-2-hydroxybenzoic acid (1.0 g, 4.64 mmol) in tetrahydrofuran (15mL) at 0 °C and the resulting mixture was stirred overnight at room temperature. After cooling to 0 °C, 0.5N hydrochloric acid (5 mL) was added dropwise followed by water (2 mL). The reaction mixture was stirred at room temperature for 30 minutes before the solvents were evaporated to dryness. The residue was partitioned between diluted aqueous sodium hydroxide solution and a 1:1 mixture of diethyl ether/hexane. Theaqueous phase was separated, acidified by addition of concentrated hydrochloric acid solution and extracted with a 1:1 mixture of diethyl ether/hexane. The organic layer was separated, dried over magnesium sulfate and the solvent was partially evaporated. The precipitate formed was filtered and dried to yield the title compound (0.75 g, 77percent) as a white solid.LRMS (mlz): 204 (M+1)+. (500 mg, 2.46 mmol) was dissolved in acetone (10 mL). p-Toluenesulfonic acid (42 mg, 0.25 mmol) was added followed by 2, 2-dimethoxypropane (1 .51 mL, 1 .23 mmol) and sodium sulfate (944 mg, 6.65 mmol). The resulting mixture was heated under vigorous stirring at 50C for 1 h. After cooling to rt, the mixture was concentrated under reduced pressure and the residue was partitioned between water and EtOAc. Theorganic layer was dried over Mg504, filtered and the solution was concentrated to dryness. The crude material was purified by column chromatography on silica gel eluting with a gradient of Cyclohexane/EtOAc from [100:0] to [90:10]. The product fractions were combined and concentrated to dryness to afford 7- bromo-2, 2-dimethyl-2, 4-dihydro-1 , 3-benzodioxine Ex.96a (456 mg, 76%) as colourless oil, which solidified to a white solid upon standing at rt. 1 H NMR (300 MHz, DMSO-d6, din ppm): 1.46 (s, 6H), 4.78 (s, 2H), 7.00 (d, 1H, J1.8Hz), 7.05 (d, 1H, J=8.lHz), 7.08 (dd, 1H, J=8.lHz, J=1.8Hz).

Molecular Weight:203.03
XLogP3:1.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:201.96294
Monoisotopic Mass:201.96294
Topological Polar Surface Area:40.5
Heavy Atom Count:10
Complexity:108
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes