3-Bromo-2-methylbenzenemethanol

methyl { (3S) -6- [ (3-bromo-2-methylbenzyl) amino] -2, 3-dihydro-l- benzofuran-3-yl } acetate; [0990][0991]Methyl 3-bromo-2-methylbenzoate (2.29 g, 10.0 mmol) was dissolved in tetrahydrofuran (50 mL) , under ice-cooling, lithium aluminum hydride (0.285 g, 7.50 mmol) was added by small portions, and the mixture was stirred under a nitrogen atmosphere for 2 hr. Sodium sulfate 10 hydrate (2.42 g, 7.50 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 2 hr. Insoluble material was filtered off through celite, and the filtrate was concentrated under reduced pressure. The obtained solid was recrystallized from heptane-ethyl acetate to give 3-bromo-2-methylbenzyl alcohol (1.76 g, yield 88percent) as colorless crystals. This product (0.943 g, 4.69 mmol) was dissolved in acetonitrile (25 mL) , a Dess-Martin reagent (2.39 g, 5.63 mmol) was added by small portions under ice-cooling, and the mixture was stirred at room temperature for 0.5 hr. The reaction mixture was treated with saturated aqueous sodium hydrogen carbonate and aqueous sodium thiosulfate solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. A solution of the obtained colorless oil, methyl [ (3S) -6-amino-2, 3-dihydro-l- benzofuran-3-yl] acetate (0.972 g, 4.69 mmol) and acetic acid(0.537 mL, 9.38 mmol) in acetonitrile (25 mL) was stirred under a nitrogen atmosphere at room temperature for 0.5 hr. Sodium triacetoxyborohydride (1.99 g, 9.38 mmol) was added to the reaction mixture, and the mixture was further stirred for 12 hr. The reaction mixture was treated with water and saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate rhexane = 5:95-40:60) to give the title compound (1.59 g, yield 87percent, 2 steps) as a colorless oil.The methyl 2-methyl-3-bromobenzoate (10 g, 43.6 mmol) was dissolved in 100 mL of absolute ethanol in an ice-water bath, After stirring, sodium borohydride (4.1 g, 10.8 mmol) was added in portions, The reaction was stirred for 1h at 0 .Remove the ice bath, heat to reflux, The reaction was carried out overnight in the reflux state.TLC shows the reaction is complete, cooled, The solvent was removed by concentration under reduced pressure, To the residue was added 50 mL of acetone, concentrated under reduced pressure to remove acetone, To the residue was added 50 mL of saturated potassium carbonate solution, The mixture was stirred at 100 ° C for 1 hour, Extracted with 50 mL x 2 chloroform, The organic phase was dried over anhydrous magnesium sulfate, filtered, The organic phase was concentrated under reduced pressure, dried, 2-methyl-3-bromobenzyl alcohol (7.39 g, yield: 84.3percent);To an ice cold solution of compound 3-Bromo-2-methylbenzaldehyde (5 g, 25 mmol) in MeOH (60 mL) was added NaBHCompound 1 (5.0 g, 23.2 mmol) was dissolved in anhydrous THF (25 mL) under argon and the reaction vessel was cooled to 0 °C in an ice bath. To this cooled solution BH3-THF complex (1M in THF, 35 mL) was added dropwise over a 3 h period. The reaction mixture was warmed to room temperature and stirred for an additional 12 h. The mixture was then poured into 1M hydrochloric acid (126 mL) and then extracted with Et20 (3 x 50 mL) . The organic extracts were combined, dried over anhydrous MgS04, filtered, and concentrated to afford the intermediate (4.6 g; 99 percent) as a colorless solid. The crude product was subjected to the subsequent reaction without further purification.3-Bromo-2-methyl-benzoic acid (20.0 g) was dissolved in anhydrous THF (200 mL) under nitrogen and the reaction vessel was cooled to 0° C. in an ice bath. To this cooled solution was added BHUnder a nitrogen atmosphere a IM solution of BHPreparative Step A; 3-Bromo-2-methyl-benzoic acid (20.0 g) was dissolved in anhydrous THF (200 mL) under nitrogen and the reaction vessel was cooled to 0° C. in an ice bath. To this cooled solution was added BHStep A. 3-Bromo-2-methyl-benzoic acid (20.0 g) was dissolved in anhydrous THF (200 mL) under nitrogen and the reaction vessel was cooled to 0°C in an ice bath. To this cooled solution was added BH(1) Synthesis of (3-bromo-2-methylphenyl)methanol [99-1] (hereinafter referred to as a compound [99-1]) 3-Bromo-2-methylbenzoic acid (1.08 g) was dissolved in tetrahydrofuran (34 mL), and to the solution was added sodium borohydride (1.15 g) under ice cooling. A solution of iodine (3.81 g) in tetrahydrofuran (16 mL) was then added to the mixture in two portions, and the mixture was stirred at room temperature for 20 hours. 4N-hydrochloric acid was added to the reaction mixture under ice cooling, and the mixture was extracted with ethyl acetate. The obtained organic layer was sequentially washed with an aqueous solution of 2N-sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (934 mg) as a white solid. Dissolved 3-bromo-2-methylbenzoic acid (8.4 g, 39.1 mmol) in tetrahydrofuran (100 mL) and cooled on ice/water. Added borane tetrahydrofuran complex (50.8 mL, 50.8 mmol) dropwise over 15-20 minutes. Stirred to room temperature over the weekend. Added 50 mL methanol dropwise to quench the excess borane. The solvent was removed by rotory evaporation. The solid was rotovaped from methanol to remove residual boron. 7.8 g of a pale yellow solid was isolated and used without further purification. 3-Bromo-2-methylbenzoic acid (30 g, 139 mmol) was dissolved in tetrahydrofuran (THF) (180 mL) and cooled to 0 °C. Lithium aluminium hydride (9.5 g, 250 mmol) was added in small portions. After stirring for 3 h, no starting material was observed by TLC. The reaction mixture was carefully quenched with ethyl acetate (20 mL) and water (20 mL). Silica gel was added and the mixture was evaporated to dryness and loaded on a small silica gel column. The product was eluted with hexane:ethyl acetate (1:1) resulting in the pure alcohol (3-bromo-2-methylphenyl)methanol (24 g) after evaporation. [00157] 3-Bromo-2-methylbenzoic acid (30 g, 139 mmol) was dissolved in tetrahydrofuran (THF) (180 mL) and cooled to 0 °C. Lithium aluminium hydride (9.5 g, 250 mmol) was added in small portions. After stirring for 3 h, no starting material was observed by TLC. The reaction mixture was carefully quenched with ethyl acetate (20 mL) and water (20 mL). Silica gel was added and the mixture was evaporated to dryness and loaded on a small silica gel column. The product was eluted with hexane:ethyl acetate (1:1) resulting in the pure alcohol (3-bromo-2- methylphenyl)methanol (24 g) after evaporation.1H NMR (600 MHz, CDCl3): 7.50 (d, 1H, J=8.1Hz), 7.29 (d, 1H, J=8.1Hz), 7.04 (t, 1H, J=8.1Hz), 4.68 (s, 2H), 2.40 (s, 3H), 1.90 (br s, 1H).13C NMR (150 MHz, CDCl3): 140.60, 135.84, 132.03, 127.12, 126.70, 126.05.To a suspension of sodium borohydride (0.630 g, 16.7 mmol) in THF (82 mL), 3-bromo-2-methylbenzoic acid (3.00 g, 14.0 mmol) was added.

Molecular Weight:201.06
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:199.98368
Monoisotopic Mass:199.98368
Topological Polar Surface Area:20.2
Heavy Atom Count:10
Complexity:105
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes