4-[(2-chloro-5-iodophenyl)methyl]phenol

Conditions: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100 mL of 4-necked flask equipped with thermometer and mechanical stirrer was charged with (2-chloro-5-iodophenyl)methanol (268.5 mg, 1 mmol), anhydrous ZnCl2 (136.3 mg, 1 mmol), dichloromethane (5.0 mL) and n-hexane (29 mL) under argon. After stirring for 10 min at 20 to 25° C., HBr (gas) was bubbled into the mixture for 10 min and a solution of phenol (197.6 mg, 2.1 mmol) in dry dichloromethane (3.0 mL) was added dropwise over 30 min. After bubbling HBr for additional 2 h, the mixture was refluxed for 3 days. The conversion was about 65%. The mixture was quenched with ice water (50 mL), extracted with ethyl acetate (2×30 mL), washed with water (2×30 mL), brine (30 mL), concentrated and the residue was purified by flash chromatography (PE:EA=25:1 as eluant, 200 mL) to give an off-white solid. Yield: 180 mg (52%). 1H NMR (CDCl3, 400 MHz): δ 7.44 (d, J=8.4 Hz, 2H), 7.03˜7.09 (m, 3H), 6.77 (d, J=8.4 Hz, 2H), 4.76 (s, 1H), 3.95 (s, 2H), 3.82 (s, 2H). MS ESI (m/z): 345 [M+1]+. 13C NMR (CDCl3, 100 MHz): δ 154.1, 141.4, 139.5, 136.6, 134.2, 131.2, 130.9, 130.1, 115.5, 91.67, 38.07. A 100 mL of 4-necked flask equipped with thermometer and mechanical stirrer HBr (gas) was bubbled into the mixture for 10 min After bubbling HBr for additional 2 h the mixture was refluxed for 3 days The mixture was quenched with ice water (50 mL) extracted with ethyl acetate (2×30 mL) washed with water (2×30 mL), brine (30 mL) concentrated the residue was purified by flash chromatography (PE:EA=25:1 as eluant, 200 mL) to give an off-white solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(2-chloro-5-iodobenzyl)phenol (8.5 g, 24.7 mmol) and triethylamine (5.0 g, 49.5 mmol) were dissolved in methylene chloride (200 mL). To the resulting mixture were added tert-butyldimethylsilane chloride (5.6 g, 37.1 mmol) and 4-(dimethylamino)pyridine (305 mg, 2.5 mmol) at 0° C. After the completion of addition, the mixture was warmed up to room temperature, and stirred for 18 hr. To the mixture was added water (100 mL). The resulting mixture was separated into an aqueous phase and an organic phase. The aqueous phase was extracted with methylene chloride (100 mL×2). The organic phases were combined, washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate, and concentrated under a reduced pressure. The resulting crude product was purified with a silica-gel column chromatography (ethyl acetate:petroleum ether=0-1:100) to produce 10.0 g of a product in a yield of 88%. After the completion of addition The resulting mixture was separated into an aqueous phase The aqueous phase was extracted with methylene chloride (100 mL×2) washed with a saturated aqueous sodium chloride solution dried over anhydrous sodium sulphate concentrated under a reduced pressure The resulting crude product was purified with a silica-gel column chromatography (ethyl acetate:petroleum ether=0-1:100)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-chloro-4-iodo-2-(4-methoxybenzyl)benzene (10.0 g, 27.9 mmol) was dissolved in methylene chloride (150 mL). To the resulting mixture was added dropwise boron tribromide (21 g, 83.7 mmol) under cooling in an ice-water bath. After the completion of dropwise addition, the mixture was warmed up to room temperature, and stirred for 3 hr. The mixture was quenched with a saturated sodium bicarbonate solution, was separated into an aqueous phase and an organic phase. The aqueous phase was extracted with methylene chloride (150 mL×2). The organic phases were combined, washed with a saturated sodium chloride solution, dried over anhydrous sodium sulphate, and concentrated under a reduced pressure. The resulting crude product was purified with a silica-gel column chromatography (ethyl acetate:petroleum ether=0-1:20) to produce 8.5 g of a product in a yield of 88%. under cooling in an ice-water bath After the completion of dropwise addition The mixture was quenched with a saturated sodium bicarbonate solution was separated into an aqueous phase The aqueous phase was extracted with methylene chloride (150 mL×2) washed with a saturated sodium chloride solution dried over anhydrous sodium sulphate concentrated under a reduced pressure The resulting crude product was purified with a silica-gel column chromatography (ethyl acetate:petroleum ether=0-1:20)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-chloro-4-iodo-2-(4-methoxybenzyl)benzene (10.0 g, 27.9 mmol) was dissolved in methylene chloride (150 mL). To the resulting mixture was added dropwise boron tribromide (21 g, 83.7 mmol) under cooling in an ice-water bath. After the completion of dropwise addition, the mixture was warmed up to room temperature, and stirred for 3 hr. The mixture was quenched with a saturated sodium bicarbonate solution, was separated into an aqueous phase and an organic phase. The aqueous phase was extracted with methylene chloride (150 mL×2). The organic phases were combined, washed with a saturated sodium chloride solution, dried over anhydrous sodium sulphate, and concentrated under a reduced pressure. The resulting crude product was purified with a silica-gel column chromatography (ethyl acetate:petroleum ether=0-1:20) to produce 8.5 g of a product in a yield of 88%. under cooling in an ice-water bath After the completion of dropwise addition The mixture was quenched with a saturated sodium bicarbonate solution was separated into an aqueous phase The aqueous phase was extracted with methylene chloride (150 mL×2) washed with a saturated sodium chloride solution dried over anhydrous sodium sulphate concentrated under a reduced pressure The resulting crude product was purified with a silica-gel column chromatography (ethyl acetate:petroleum ether=0-1:20)

Conditions: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100 mL of 4-necked flask equipped with thermometer and mechanical stirrer was charged with (2-chloro-5-iodophenyl)methanol (268.5 mg, 1 mmol), anhydrous ZnCl2 (136.3 mg, 1 mmol), dichloromethane (5.0 mL) and n-hexane (29 mL) under argon. After stirring for 10 min at 20 to 25° C., HBr (gas) was bubbled into the mixture for 10 min and a solution of phenol (197.6 mg, 2.1 mmol) in dry dichloromethane (3.0 mL) was added dropwise over 30 min. After bubbling HBr for additional 2 h, the mixture was refluxed for 3 days. The conversion was about 65%. The mixture was quenched with ice water (50 mL), extracted with ethyl acetate (2×30 mL), washed with water (2×30 mL), brine (30 mL), concentrated and the residue was purified by flash chromatography (PE:EA=25:1 as eluant, 200 mL) to give an off-white solid. Yield: 180 mg (52%). 1H NMR (CDCl3, 400 MHz): δ 7.44 (d, J=8.4 Hz, 2H), 7.03˜7.09 (m, 3H), 6.77 (d, J=8.4 Hz, 2H), 4.76 (s, 1H), 3.95 (s, 2H), 3.82 (s, 2H). MS ESI (m/z): 345 [M+1]+. 13C NMR (CDCl3, 100 MHz): δ 154.1, 141.4, 139.5, 136.6, 134.2, 131.2, 130.9, 130.1, 115.5, 91.67, 38.07. A 100 mL of 4-necked flask equipped with thermometer and mechanical stirrer HBr (gas) was bubbled into the mixture for 10 min After bubbling HBr for additional 2 h the mixture was refluxed for 3 days The mixture was quenched with ice water (50 mL) extracted with ethyl acetate (2×30 mL) washed with water (2×30 mL), brine (30 mL) concentrated the residue was purified by flash chromatography (PE:EA=25:1 as eluant, 200 mL) to give an off-white solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(2-chloro-5-iodobenzyl)phenol (8.5 g, 24.7 mmol) and triethylamine (5.0 g, 49.5 mmol) were dissolved in methylene chloride (200 mL). To the resulting mixture were added tert-butyldimethylsilane chloride (5.6 g, 37.1 mmol) and 4-(dimethylamino)pyridine (305 mg, 2.5 mmol) at 0° C. After the completion of addition, the mixture was warmed up to room temperature, and stirred for 18 hr. To the mixture was added water (100 mL). The resulting mixture was separated into an aqueous phase and an organic phase. The aqueous phase was extracted with methylene chloride (100 mL×2). The organic phases were combined, washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate, and concentrated under a reduced pressure. The resulting crude product was purified with a silica-gel column chromatography (ethyl acetate:petroleum ether=0-1:100) to produce 10.0 g of a product in a yield of 88%. After the completion of addition The resulting mixture was separated into an aqueous phase The aqueous phase was extracted with methylene chloride (100 mL×2) washed with a saturated aqueous sodium chloride solution dried over anhydrous sodium sulphate concentrated under a reduced pressure The resulting crude product was purified with a silica-gel column chromatography (ethyl acetate:petroleum ether=0-1:100)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-chloro-4-iodo-2-(4-methoxybenzyl)benzene (10.0 g, 27.9 mmol) was dissolved in methylene chloride (150 mL). To the resulting mixture was added dropwise boron tribromide (21 g, 83.7 mmol) under cooling in an ice-water bath. After the completion of dropwise addition, the mixture was warmed up to room temperature, and stirred for 3 hr. The mixture was quenched with a saturated sodium bicarbonate solution, was separated into an aqueous phase and an organic phase. The aqueous phase was extracted with methylene chloride (150 mL×2). The organic phases were combined, washed with a saturated sodium chloride solution, dried over anhydrous sodium sulphate, and concentrated under a reduced pressure. The resulting crude product was purified with a silica-gel column chromatography (ethyl acetate:petroleum ether=0-1:20) to produce 8.5 g of a product in a yield of 88%. under cooling in an ice-water bath After the completion of dropwise addition The mixture was quenched with a saturated sodium bicarbonate solution was separated into an aqueous phase The aqueous phase was extracted with methylene chloride (150 mL×2) washed with a saturated sodium chloride solution dried over anhydrous sodium sulphate concentrated under a reduced pressure The resulting crude product was purified with a silica-gel column chromatography (ethyl acetate:petroleum ether=0-1:20)