4-Bromo-3-methoxybenzenemethanol

To a solution of 3-methoxybenzyl alcohol (20.0 g, 145 mmol) in THF (400 mL) was added N-bromosuccinimide (26 g, 146 mmol) and the resultant mixture was stirred at room temperature for 8 h. Ether (500 mL) was added and the mixture was washed with water (3×100 mL). The solution was dried over magnesium sulfate and concentrated to afford the title compound (31.2 g, 99percent) which was used as such for the next step.The compound 3-methoxybenzyl alcohol (10 g, 72.4 mmol) was dissolved in a mixture of acetonitrile (250 mL) and water (250 mL) and then sodium bromate (19.1 g, 127 mmol) and sodium bisulfite (13.2 g, 127 mmol) were added. Method 10E: using the appropriate benzyl alcohol.Aromatic Bromination of the Benzyl AlcoholThe benzyl alcohol was dissolved in an equivolumetric acetonitrile/water mixture. Potassium bromide, then sodium hydrogenosulfite were added and the reaction mixture was stirred at room temperature for 1 h30. A sodium bisulfate 10percent solution was a added and the mixture was extracted with diethyl ether. The organic layer was washed with a saturated sodium carbonate solution, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The product was chromatographed over silica gel.10.8.1 To a mixture of methyl 4-bromo-3-methoxy-benzoate (3.00 g, 12.24 mmol) in THF (40) was added LiAlHTo a mixture of A-26 (3.00 g, 12.24 mmol) in THF (40 mL) was added LiAlH4 (1.39 g, 36.72 mmol) at -40C under N2, and the mixture was stirred at -40C for 2 hours. To the mixture was added _0 (1.76 g) dropwise at -40 C, and the mixture was stirred at 0 C for 0.5 hour, followed by stirring at 50 C for 0.5 hour. The mixture was then filtered through Celite, eluted by THF (100 mL x 2), concentrated, dissolved in EtOAc (200 mL), washed with water (30 mL x 2) and brine (50 mL), dried over Na2S04, filtered and concentrated to give A-27 (2.50 g, 11.52 mmol) as an oil. 1H NMR (400MHz DMSO-d6) _ = 7.49 (d, 1H), 7.06 (s, 1H), 6.84 (d, 1H), 5.29 (t, 1H), 4.47 (d, 2H), 3.83 (s, 3H).Compound 9-e (2.16 g, 10 mmol) and p-toluenesulfonic acid (1.72 g, 1 mmol) were added to dichloromethane (50 mL), followed by slow addition of 3, 4-dihydropyran (1.64 g, 20 mmol) and the resultant was stirred at room temperature for 3 hours. The reaction solution was concentrated under reduced pressure, quenched with saturated aqueous sodium bicarbonate solution (50 mL) and the mixture was extracted with dichloromethane (50 mL×3). The combined organic phase was dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was added directly to anhydrous tetrahydrofuran (10 mL) pre-cooled to '78° C., followed by the dropwise addition of n-butyllithium in n-hexane (5 mL, 12.5 mmol). After stirring for 2 hours, trimethyl borate (1.3 g, 12.5 mmol) was added to the reaction solution. The reaction mixture was slowly warmed to room temperature and further stirred for 2 hours. The reaction was quenched with water (50 mL) and sodium hydroxide (0.8 g, 20 mmol) and extracted with ethyl acetate (50 mL×3). The aqueous phase is adjusted to pH=7 with 1M aqueous hydrochloric acid solution and then extracted with ethyl acetate (50 mL×3). The organic phase was concentrated under reduced pressure to give 9-d as a yellow solid (2.1 g, yield 72.7percent). LC-MS (ESI): m/z=289[M+H]+.

Molecular Weight:217.06
XLogP3:1.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:215.97859
Monoisotopic Mass:215.97859
Topological Polar Surface Area:29.5
Heavy Atom Count:11
Complexity:119
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes