1-chloro-4-iodo-2-[(4-methoxyphenyl)methyl]benzene

Conditions: temp:-3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 mL of 4-neck flask equipped with an internal thermometer and a condenser were added anisole (5.7 g, 52.0 mmol) and dichloromethane (17 mL) and the mixture was cooled to −3° C. Aluminum (III) chloride (7.4 g, 55.0 mmol) was added to the above solution over 1 h while maintaining the internal temperature below 5° C. After the addition was completed, the mixture was stirred for 30 min at 0˜5° C., and a solution of 2-chloro-5-iodobenzoyl chloride (15.0 g, 0.05 mol) in dichloromethane (15 mL) was added dropwise over 1 hour while maintaining the internal temperature below 5° C. The mixture was stirred for another 1 hour at 0˜5° C. and warmed to 10˜15° C. PMHS (15.0 g, 0.25 mol) was added dropwise while maintaining the internal temperature below 25° C. After stirring for 10 hours at 25° C., additional PMHS (9.0 g, 0.15 mol) was added to the above mixture. After stirring for another 16 hours at 30° C., the mixture was cooled to 5˜10° C. and ice water (100 mL) was added slowly dropwise over 1 hour with stirring. Note: A severe exotherm would occur upon addition of the first portion of water. The mixture was filtered and the filter cake was slurried with dichloromethane (100 mL) containing diatomite (30 g). The mixture was filtered and the filter cake was washed with dichloromethane (2×50 mL). The combined organic layers were washed with brine (100 mL). After removal of the volatiles, the residue was recrystallized from absolute ethanol (58 mL) to give 12.0 g of 1-chloro-4-iodo-2-(4-methoxybenzyl)benzene as a white solid (yield, 67%, HPLC-0002: 98.7%). Note: The purity can be increased by doing a second recrystallization of 1-chloro-4-iodo-2-(4-methoxybenzyl)benzene, HPLC purity could be up to 99.5% with 75˜80% yield. 1H NMR (CDCl3, 400 MHz): δ 7.50 (d, J=8.4 Hz, 2H), 7.10˜7.13 (m, 3H), 6.88 (d, J=8.4 Hz, 2H), 4.00 (s, 2H), 3.82 (s, 3H). MS ESI (m/z): 357 [M+1]+. 13C NMR (CDCl3, 100 MHz): δ 158.3, 141.5, 139.5, 136.6, 134.2, 131.2, 130.6, 129.9, 114.1, 91.71, 55.29, 38.09. A 250 mL of 4-neck flask equipped with an internal thermometer and a condenser while maintaining the internal temperature below 5° C After the addition while maintaining the internal temperature below 5° C The mixture was stirred for another 1 hour at 0˜5° C. warmed to 10˜15° C while maintaining the internal temperature below 25° C After stirring for 10 hours at 25° C. After stirring for another 16 hours at 30° C. the mixture was cooled to 5˜10° C. with stirring The mixture was filtered containing diatomite (30 g) The mixture was filtered the filter cake was washed with dichloromethane (2×50 mL) The combined organic layers were washed with brine (100 mL) After removal of the volatiles the residue was recrystallized from absolute ethanol (58 mL) to give

Conditions: temp:-3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 mL of 4-neck flask equipped with an internal thermometer and a condenser were added anisole (5.7 g, 52.0 mmol) and dichloromethane (17 mL) and the mixture was cooled to −3° C. Aluminum (III) chloride (7.4 g, 55.0 mmol) was added to the above solution over 1 h while maintaining the internal temperature below 5° C. After the addition was completed, the mixture was stirred for 30 min at 0˜5° C., and a solution of 2-chloro-5-iodobenzoyl chloride (15.0 g, 0.05 mol) in dichloromethane (15 mL) was added dropwise over 1 hour while maintaining the internal temperature below 5° C. The mixture was stirred for another 1 hour at 0˜5° C. and warmed to 10˜15° C. PMHS (15.0 g, 0.25 mol) was added dropwise while maintaining the internal temperature below 25° C. After stirring for 10 hours at 25° C., additional PMHS (9.0 g, 0.15 mol) was added to the above mixture. After stirring for another 16 hours at 30° C., the mixture was cooled to 5˜10° C. and ice water (100 mL) was added slowly dropwise over 1 hour with stirring. Note: A severe exotherm would occur upon addition of the first portion of water. The mixture was filtered and the filter cake was slurried with dichloromethane (100 mL) containing diatomite (30 g). The mixture was filtered and the filter cake was washed with dichloromethane (2×50 mL). The combined organic layers were washed with brine (100 mL). After removal of the volatiles, the residue was recrystallized from absolute ethanol (58 mL) to give 12.0 g of 1-chloro-4-iodo-2-(4-methoxybenzyl)benzene as a white solid (yield, 67%, HPLC-0002: 98.7%). Note: The purity can be increased by doing a second recrystallization of 1-chloro-4-iodo-2-(4-methoxybenzyl)benzene, HPLC purity could be up to 99.5% with 75˜80% yield. 1H NMR (CDCl3, 400 MHz): δ 7.50 (d, J=8.4 Hz, 2H), 7.10˜7.13 (m, 3H), 6.88 (d, J=8.4 Hz, 2H), 4.00 (s, 2H), 3.82 (s, 3H). MS ESI (m/z): 357 [M+1]+. 13C NMR (CDCl3, 100 MHz): δ 158.3, 141.5, 139.5, 136.6, 134.2, 131.2, 130.6, 129.9, 114.1, 91.71, 55.29, 38.09. A 250 mL of 4-neck flask equipped with an internal thermometer and a condenser while maintaining the internal temperature below 5° C After the addition while maintaining the internal temperature below 5° C The mixture was stirred for another 1 hour at 0˜5° C. warmed to 10˜15° C while maintaining the internal temperature below 25° C After stirring for 10 hours at 25° C. After stirring for another 16 hours at 30° C. the mixture was cooled to 5˜10° C. with stirring The mixture was filtered containing diatomite (30 g) The mixture was filtered the filter cake was washed with dichloromethane (2×50 mL) The combined organic layers were washed with brine (100 mL) After removal of the volatiles the residue was recrystallized from absolute ethanol (58 mL) to give

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:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2-chloro-5-iodophenyl)(4-methoxyphenyl)methanone (12.0 g, 32.2 mmol) and triethyl silane (9.86 g, 84.8 mmol) were dissolved in acetonitrile (200 mL). To the resulting mixture was added boron trifluoride-diethyl etherate complex (13.7 g, 96.5 mmol) at 0° C. After the completion of dropwise addition, the mixture was warmed up to 70° C., and stirred for 3 hr. Then the mixture was cooled to room temperature. The mixture was quenched with a saturated sodium bicarbonate solution, and extracted with ethyl acetate (200 mL×3). 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=0-1:100) to produce 10.0 g of a product in a yield of 87%. After the completion of dropwise addition Then the mixture was cooled to room temperature The mixture was quenched with a saturated sodium bicarbonate solution extracted with ethyl acetate (200 mL×3) 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=0-1:100)

Conditions: temp:-3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 mL of 4-neck flask equipped with an internal thermometer and a condenser were added anisole (5.7 g, 52.0 mmol) and dichloromethane (17 mL) and the mixture was cooled to −3° C. Aluminum (III) chloride (7.4 g, 55.0 mmol) was added to the above solution over 1 h while maintaining the internal temperature below 5° C. After the addition was completed, the mixture was stirred for 30 min at 0˜5° C., and a solution of 2-chloro-5-iodobenzoyl chloride (15.0 g, 0.05 mol) in dichloromethane (15 mL) was added dropwise over 1 hour while maintaining the internal temperature below 5° C. The mixture was stirred for another 1 hour at 0˜5° C. and warmed to 10˜15° C. PMHS (15.0 g, 0.25 mol) was added dropwise while maintaining the internal temperature below 25° C. After stirring for 10 hours at 25° C., additional PMHS (9.0 g, 0.15 mol) was added to the above mixture. After stirring for another 16 hours at 30° C., the mixture was cooled to 5˜10° C. and ice water (100 mL) was added slowly dropwise over 1 hour with stirring. Note: A severe exotherm would occur upon addition of the first portion of water. The mixture was filtered and the filter cake was slurried with dichloromethane (100 mL) containing diatomite (30 g). The mixture was filtered and the filter cake was washed with dichloromethane (2×50 mL). The combined organic layers were washed with brine (100 mL). After removal of the volatiles, the residue was recrystallized from absolute ethanol (58 mL) to give 12.0 g of 1-chloro-4-iodo-2-(4-methoxybenzyl)benzene as a white solid (yield, 67%, HPLC-0002: 98.7%). Note: The purity can be increased by doing a second recrystallization of 1-chloro-4-iodo-2-(4-methoxybenzyl)benzene, HPLC purity could be up to 99.5% with 75˜80% yield. 1H NMR (CDCl3, 400 MHz): δ 7.50 (d, J=8.4 Hz, 2H), 7.10˜7.13 (m, 3H), 6.88 (d, J=8.4 Hz, 2H), 4.00 (s, 2H), 3.82 (s, 3H). MS ESI (m/z): 357 [M+1]+. 13C NMR (CDCl3, 100 MHz): δ 158.3, 141.5, 139.5, 136.6, 134.2, 131.2, 130.6, 129.9, 114.1, 91.71, 55.29, 38.09. A 250 mL of 4-neck flask equipped with an internal thermometer and a condenser while maintaining the internal temperature below 5° C After the addition while maintaining the internal temperature below 5° C The mixture was stirred for another 1 hour at 0˜5° C. warmed to 10˜15° C while maintaining the internal temperature below 25° C After stirring for 10 hours at 25° C. After stirring for another 16 hours at 30° C. the mixture was cooled to 5˜10° C. with stirring The mixture was filtered containing diatomite (30 g) The mixture was filtered the filter cake was washed with dichloromethane (2×50 mL) The combined organic layers were washed with brine (100 mL) After removal of the volatiles the residue was recrystallized from absolute ethanol (58 mL) to give

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:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2-chloro-5-iodophenyl)(4-methoxyphenyl)methanone (12.0 g, 32.2 mmol) and triethyl silane (9.86 g, 84.8 mmol) were dissolved in acetonitrile (200 mL). To the resulting mixture was added boron trifluoride-diethyl etherate complex (13.7 g, 96.5 mmol) at 0° C. After the completion of dropwise addition, the mixture was warmed up to 70° C., and stirred for 3 hr. Then the mixture was cooled to room temperature. The mixture was quenched with a saturated sodium bicarbonate solution, and extracted with ethyl acetate (200 mL×3). 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=0-1:100) to produce 10.0 g of a product in a yield of 87%. After the completion of dropwise addition Then the mixture was cooled to room temperature The mixture was quenched with a saturated sodium bicarbonate solution extracted with ethyl acetate (200 mL×3) 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=0-1:100)