2-Chloro-5-iodobenzyl bromide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of potassium carbonate (4.30 g, 53.3 mmol) in N,N-dimethylformamide (47 mL) and methanol (5 mL) at 50° C. was added a solution of 2-(bromomethyl)-1-chloro-4-iodobenzene (i.e. the product of Step A) (5.20 g, 15.7 mmol) in N,N-dimethylformamide (10 mL). The reaction mixture was heated at 110° C. for 1 h and then cooled to room temperature. The reaction mixture was partitioned between diethyl ether (200 mL) and water (200 mL), the organic layer was separated, washed with water (3×50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound as a yellow oil (4.32 g). cooled to room temperature The reaction mixture was partitioned between diethyl ether (200 mL) and water (200 mL) the organic layer was separated washed with water (3×50 mL) dried over magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: To a mixture of 2-chloro-5-iodotoluene (4.07 g, 16.12 mmol), N-bromosuccinimide (3.16 g, 17.73 mmol) in dichloromethane (258 mL) and water (258 mL) was added 2,2′-azodiisobutyronitrile (0.132 g, 0.81 mmol). The reaction mixture was irradiated with a halogen sun lamp (150 watt) for 2 h and then cooled to room temperature. The two-phase reaction mixture was separated, and the aqueous layer was extracted with dichloromethane (50 mL). The combined organic layers were washed with water (2×150 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound as an orange oil (5.20 g). The reaction mixture was irradiated with a halogen sun lamp (150 watt) for 2 h The two-phase reaction mixture was separated the aqueous layer was extracted with dichloromethane (50 mL) The combined organic layers were washed with water (2×150 mL) dried over magnesium sulfate filtered concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of potassium carbonate (4.30 g, 53.3 mmol) in N,N-dimethylformamide (47 mL) and methanol (5 mL) at 50° C. was added a solution of 2-(bromomethyl)-1-chloro-4-iodobenzene (i.e. the product of Step A) (5.20 g, 15.7 mmol) in N,N-dimethylformamide (10 mL). The reaction mixture was heated at 110° C. for 1 h and then cooled to room temperature. The reaction mixture was partitioned between diethyl ether (200 mL) and water (200 mL), the organic layer was separated, washed with water (3×50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound as a yellow oil (4.32 g). cooled to room temperature The reaction mixture was partitioned between diethyl ether (200 mL) and water (200 mL) the organic layer was separated washed with water (3×50 mL) dried over magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: To a mixture of 2-chloro-5-iodotoluene (4.07 g, 16.12 mmol), N-bromosuccinimide (3.16 g, 17.73 mmol) in dichloromethane (258 mL) and water (258 mL) was added 2,2′-azodiisobutyronitrile (0.132 g, 0.81 mmol). The reaction mixture was irradiated with a halogen sun lamp (150 watt) for 2 h and then cooled to room temperature. The two-phase reaction mixture was separated, and the aqueous layer was extracted with dichloromethane (50 mL). The combined organic layers were washed with water (2×150 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound as an orange oil (5.20 g). The reaction mixture was irradiated with a halogen sun lamp (150 watt) for 2 h The two-phase reaction mixture was separated the aqueous layer was extracted with dichloromethane (50 mL) The combined organic layers were washed with water (2×150 mL) dried over magnesium sulfate filtered concentrated under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Bromomethyl-2-chloro-5-iodo-benzene (60) (400 mg, 1.2 mmol) and potassium phthalimide (693 mg, 1.5 mmol) were stirred in dry DMF (20 mL) and heated to 80° C. for 3 hours. After cooling, the suspension was filtered and concentrated in vacuo, and the residue was partitioned between water (30 mL) and Et2O (30 mL). The aqueous phase was extracted with ether (20 mL×3). The combined organic phases were dried over Na2SO4, filtered and concentrated to give 63 (455 mg, 95%). 1H NMR (CDCl3, 300 MHz) δ 7.92-7.86 (m, 2H), 7.78-7.75 (m, 2H), 7.54-7:50 (m, 2H), 7.10 (d, J=8.4 Hz, 1H), 4.93 (s, 2H). MS (m/e) (API-ES) 397.9 (M)+, m.p. 134-136° C. After cooling the suspension was filtered concentrated in vacuo the residue was partitioned between water (30 mL) and Et2O (30 mL) The aqueous phase was extracted with ether (20 mL×3) The combined organic phases were dried over Na2SO4 filtered concentrated

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

Procedure: A mixture of 2-chloro-5-iodo-toluene (0.5 g, 1.98 mmol), N-bromosuccinimide (0.422 g, 2.35 mmol) and benzoyl peroxide (21.5 mg, 0.089 mmol) in dry CCl4 (5 mL) was stirred and heated to reflux for 3 h. After cooling, the mixture-was filtered, and the red filtrate was washed with a saturated solution of sodium thiosulfate (2×10 mL). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (petroleum ether), to give 60 as a white solid (361 mg, 55%). 1H NMR (CDCl3, 300 MHz) δ 7.76 (d, J=2.4 Hz, 1H), 7.56 (dd, J=8.7, 2.1 Hz, 1H), 7.12 (d, J=8.4 Hz, 1H), 4.49 (s, 2H). MS (m/e) (positive FAB) 332.1 (M+H)+, m.p. 94-95° C. heated to reflux for 3 h After cooling the mixture-was filtered the red filtrate was washed with a saturated solution of sodium thiosulfate (2×10 mL) The organic phase was washed with brine dried over Na2SO4 filtered concentrated The residue was purified by flash chromatography on silica gel (petroleum ether)