2-BROMO-5-IODOBENZYL ALCOHOL

Tetrahydrofuran (99.7g) and sodium borohydride (15.2g, 0.4mol) were added to the reaction flask at 10-25°C.A solution of 2-bromo-5-iodobenzoic acid (109.4 g, 0.34 mol, prepared in Example 2) in tetrahydrofuran (151 g) was slowly added dropwise.At 10-30°C, a solution of sulfuric acid (16.4 g) in tetrahydrofuran (25 g) was added dropwise to the reaction vessel. After the addition was completed, the reaction was performed at room temperature for 2 hours. Then, it was heated to reflux 66°C, refluxed for 2 hours, and then lowered to room temperature. 5percent hydrochloric acid (235 g) was slowly added dropwise and THF was distilled off under reduced pressure (-0.01 MPa).Add 326.7 g of MTBE and 222.7 g of water to dissolve the solid, cool to 15-25°C, separate the layers, and evaporate the organic layer under reduced pressure (-0.095 MPa).Toluene (108.8 g) and water (108.8 g) were added and the mixture was warmed to 60°C for 1 h, reduced to 18-22°C and filtered. After drying, 89.1 g of an off-white solid product was obtained with a measured content of >99percent and a yield of 85.1percent.To a 5000-mL 4-necked round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed 2-bromo-5-iodobenzoic acid (200 g, 61 1.78 mmol, 1.00 equiv) and tetrahydrofuran (1500 mL), followed by the addition of borane (1834 mL, 3.00 equiv) dropwise with stirring at 0 °C. The resulting solution was stirred for 4 h at room temperature, quenched by the addition of 4000 mL of water/ice, and then extracted with 2x2000 mL of ethyl acetate. The combined organic layer was washed with 2x2000 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was diluted with 500 mL of PE. The solids were collected by filtration to afford 160 g (84percent) of (2-bromo-5-iodophenyl)methanol as a white solid.Step 2: (2-bromo-5-iodophenyl)methanolTo a solution of 2-bromo-5-iodobenzaldehyde (12.4 g, 40 mmol) in MeOH (50 mL) was added NaBHA 100 mL single-necked flask was charged with 1 (5 g, 0.016 mol), camphorsulfonic acid (350 mg, 1.5 mmol) and dissolved in 50 mL of methylene chloride. THP-OH (3 ml, 0.032 mol) was added slowly and stirred for 40 minutes. The reaction was complete by TLC and concentrated directly to give Intermediate 2 (3 g, 47percent yield).To a 3000-mL 4-necked round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed To a stirred solution of

Molecular Weight:312.93
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:311.86467
Monoisotopic Mass:311.86467
Topological Polar Surface Area:20.2
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes