5-Bromo-1,3-benzenedimethanol

4-(3, 5-Bis-[(S)-2-methylidene-7-dimethoxy-1, 2, 3, 11a-tetrahydro-pyrrolo[2, 1c][1, 4] benzodiazepin-5-one-8-yloxymethyl]-phenyl)-propanoic acid N-hydroxysuccinimide ester [Show Image]Compound 2: To a suspension of lithium aluminum hydride 2.19 g, 54.8 mmol) in anhydrous THF (50 mL) was added solution of dimethyl 5-bromoisophthalate (9.98 g, 36.5 mmol) in THF (100 mL) at 0°C during 1 h period. After completion of addition, the mixture was stirred at rt for 2 h. Upon that time, 150 mL of THF was added. The mixture was re-cooled to 0°C and quenched with saturated aqueous NaCl. The white precipitate was filtered off, and the solid was further washed with extra THF (100 mL). Combined THF solution was dried with NaTo a vigorously stirred suspension of lithium aluminium hydride (7.2g, 190mmol) in anhydrous tetrahydrofuran (500ml), maintained at ~0°C in an ice bath, was added dropwise a solution of dimethyl 5-bromoisophthalate (23.6g, 86.5mmol) in anhydrous tetrahydrofuran (100ml) over 2hr, and the reaction mixture then allowed to attain ambient temperature while stirring vigorously overnight. To this was then added dropwise, deionised water (7.2ml) followed by sodium hydroxide solution (3M, 7.2ml) followed by further deionised water (21.6ml). The pale grey precipitate was removed from the clear, colourless supernatant by filtration and solvent removed in vacuo to yield the title compound (15.3g, 70.6mmol) as a white, crystalline solid. δ (de-DMSO): 6.96 (s, 2H, Arom.C5-bromoisophtalic acid (25.0 gram, 0.102 mol, 1 equiv) was dissolved in dry THF (500 mL) at 0 °C under argon atmosphere. 10M Borane dimethylsulfide complex (50 mL, 0.50 mmol, 5 equiv) was added and the mixture was stirred at room temperature overnight. H20 (1000 mL) was added carefully to the mixture followed by addition of EtOAc (1000 mL). After separation of the layers, the organic layer was washed with H20 (3 >< 750 mL) and brine (1000 mL). The organic layer was dried over MgSO4, filtered and (0296) concentrated in racuo yielding alcohol 7 as a white powder in 85percent yield with no need for further purification. 1H NMR (400 MHz, DMSO) 8 7.36 (s, 2H), 7.25 (s, 1H), 5.30 (t, 2H), 4.48 (d, 4H). 13C NMR (400 MHZ, DMSO) 6 145.2, 127.1, 123.1, 121.3, 62.1. IR V 3210, 2851, 1602, 1419 cm-1. HRMS (FD+) m/z caIcuIated for C8H9BrOz 215.9786, found 215.9798. Spectral data in agreement with reported data (Wytko and Weiss, 1994).A solution of 5-bromoisophthalic acid (5 g, 20.4 mmol) in tetrahydrofuran (80 ml) was added to a solution of sodium borohydride (2.76 g, 73.0 mmol) in tetrahydrofuran (20 ml) under an argon atmosphere and ice cooling, followed by stirring. Boron trifluoride diethyl ether complex (7.6 ml, 60.9 mmol) was added over 1 hour while cooling on ice, and the temperature was returned to room temperature and stirred for 1 hour. A 0.5 mol/l sodium hydroxide aqueous solution (40 ml) was added to the reaction solution, and the mixture was extracted with ethyl acetate. The aqueous layer was further extracted twice with ethyl acetate, the organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified on a column to give (5-bromo-1, 3-phenylene) dimethanol (3.60 g, 81percent) as a white solid.A three-necked flask having a capacity of 2 liters was charged with 109.2g of dimethyl 5-bromo-isophthalate and then with 400 ml of tetrahydrofuran (THF), to prepare a solution of dimethyl 5-bromoisophthalate. The solution was mixed with 16.6g of sodium borohydride and the resultant mixture liquid was agitated while cooling the mixture liquid with ice pieces. Separately, 40.5 ml of methyl alcohol were dissolved in 150 ml of THF, the resultant solution was mixed in the ice-cooled mixture liquid. Then, the resultant reaction mixture liquid was agitated for 5 hours while cooling with ice pieces. The reaction mixture liquid was added with 380 ml of water to terminate the reaction, and then mixed with a 1 mole hydrochloric acid solution to adjust the pH value of the reaction mixture liquid to 7.0. The resultant reaction mixture liquid was subjected to an extraction treatment with 380 ml of ethyl acetate and then with 200 ml of ethyl acetate. The resultant organic extract liquids were mixed with each other, and the resultant mixed extract liquid was washed with 300 ml of water and then with 80 ml of a saturated aqueous common salt solution, and the resultant washed extract liquid was dried with a drying agent consisting of anhydrous magnesium sulfate. The dried extract liquid was filtered to separate the drying agent, and the resultant filtrate was concentrated. A crude product of the target compound, namely methyl 5-bromo-3-(hydroxymethyl)benzoate was obtained in an amount of 96.5g. In the crude product, the mass ratio of the target compound, namely methyl 5-bromo-3-(hydroxymethyl)benzoate to the by-product consisting of 5-bromo-3-(hydroxymethyl)benzyl alcohol was 88:10, as determined by NMR measurement. The crude product was dissolved in 160 ml of methyl alcohol; the resultant solution was placed in a separatory funnel and mixed with 160 ml of water and 1000 ml of xylene; and the resultant mixture liquid was subjected to a phase separation. The resultant organic phase fraction was collected, washed with 160 ml of a solution of methyl alcohol in water in volume ratio of 1:1, then with 160 ml of water and finally with 160 ml of a saturated aqueous common salt solution. The washed organic phase fraction was dried with a drying agent consisting of anhydrous magnesium sulfate. The dried solution was subjected to a filtration procedure to remove the drying agent from the organic phase fraction. Then, the filtrate was concentrated. The target compound, namely, purified methyl 5-bromo-3-(hydroxymethyl)benzoate was obtained in an amount of 81.98g. The yield thereof was 83.3percent. In the resultant purified product, a mass ratio of the target compound, methyl 5-bromo-3-(hydroxymethyl)benzoate to a by-product, namely, 5-bromo-3-(hydroxymethyl)benzyl alcohol was 96:1.8, determined by the NMR measurement. The results of the 1H-NMR measurement (200 MHz, δ ppm, CDCl3) were as follows 3.93(s, 3H), 4.74 (d, J = 5.6 Hz, 2H) 7.73 (s, 1H), 7.95 (s, 1H), 8.09 (s, 1H).Compound 3: compound 2 (3.36 g, 15.5 mmol) was suspended in anhydrous CH2Cl2 (31 mL). TBSCl (5.14 g, 34.1 mmol) was added, followed by imidazole (3.16 g, 46.5 mmol). The mixture was stirred at rt for 1 h. The white precipitate was filtered off and the filtrate was concentrated with rotavapor. The resulting residue was purified by flash chromatography (silica gel, 97:3 hexanes/EtOAc) to give 3 as colorless oil (6.15 g, 89%): 1HNMR (300 MHz, CDCl3) delta 0.081 (s, 12H), 0.92 (s, 18H), 4.67 (s, 4H), 7.18 (s, 1H), 7.31 (s, 2H).

Molecular Weight:217.06
XLogP3:0.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:215.97859
Monoisotopic Mass:215.97859
Topological Polar Surface Area:40.5
Heavy Atom Count:11
Complexity:107
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes