5-bromo-2-iodobenzaldehyde

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

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

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

Procedure: To an ice-cold solution of 2,2,5,5-tetramethyldihydrofuran-3-one (0.388 g, 2.73 mmoles) in anhydrous 1,2-dimethoxyethane (5 ml) is added sodium methoxide (0.177 g, 3.27 mmoles) in one portion. The reaction mixture is stirred for 5 minutes at this temperature, followed by the dropwise addition of 5-bromo-2-iodo-benzaldehyde (0.850 g, 2.73 mmoles) as a solution in 1,2-dimethoxyethane (5 ml). The reaction mixture is further stirred at 0° C. for 30 minutes, then at ambient temperature for a 1 hour. After partitioning between 1M hydrochloric acid and dichloromethane, the organic phase is separated, and the aqueous phase is extracted again with additional dichloromethane. All organics are combined then concentrated in vacuo to afford 4-[1-(5-bromo-2-iodophenyl)methylidene]-2,2,5,5-tetramethyldihydrofuran-3-one (1.18 g) as a yellow gum. The reaction mixture is further stirred at 0° C. for 30 minutes at ambient temperature for a 1 hour After partitioning between 1M hydrochloric acid and dichloromethane the organic phase is separated the aqueous phase is extracted again with additional dichloromethane All organics are combined then concentrated in vacuo

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

Procedure: To a solution of 5-bromo-2-iodobenzonitrile (5.00 g, 16.00 mmoles) in anhydrous tetrahydrofuran (80 ml) at −80° C. is added diisobutyl aluminium hydride (16.0 ml, 16.0 mmoles, 1M solution in toluene) dropwise over 10 minutes. The reaction mixture is stirred at −80° C. for a 1 hour, then allowed to warm to ambient temperature and stir overnight. Additional diisobutyl aluminium hydride (16.0 ml, 16.0 mmoles, 1M solution in toluene) is next added dropwise at room temperature, and the reaction mixture further stirred for 1 hour. After careful quenching with 2M hydrochloric acid (cooling in ice bath), the crude product is extracted with ethyl acetate (×2), then all organics are combined and dried over magnesium sulfate and filtered. The filtrate is evaporated under reduced pressure then purified by flash column chromatography (isohexane to 10% ethyl acetate in isohexane eluant) to afford 5-bromo-2-iodobenzaldehyde (0.85 g). to warm to ambient temperature stir overnight the reaction mixture further stirred for 1 hour After careful quenching with 2M hydrochloric acid (cooling in ice bath) the crude product is extracted with ethyl acetate (×2) dried over magnesium sulfate filtered The filtrate is evaporated under reduced pressure then purified by flash column chromatography (isohexane to 10% ethyl acetate in isohexane eluant)

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

Procedure: A mixture of 5-bromo-2-iodobenzaldehyde (1.0 g, 3.2 mmol) and PTSA (0.1 g) in ethanol was stirred under reflux for 18 hrs and concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with saturated NaHCO3, dried over anhydrous Na2SO4 and concentrated to give 4-bromo-2-(diethoxymethyl)-1-iodobenzene (16.10) that was directly used in next reaction without further purification. under reflux for 18 hrs concentrated under reduced pressure The residue was dissolved in ethyl acetate washed with saturated NaHCO3 dried over anhydrous Na2SO4 concentrated

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

Procedure: A mixture of 5-bromo-2-iodobenzaldehyde (14.9) (1.0 g, 3.2 mmol) and PTSA (0.1 g) in ethanol was stirred under reflux for 18 hrs and concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with saturated NaHCO3, dried over anhydrous Na2SO4 and concentrated to give 4-bromo-2-(diethoxymethyl)-1-iodobenzene (14.10) that was directly used in next reaction without further purification. under reflux for 18 hrs concentrated under reduced pressure The residue was dissolved in ethyl acetate washed with saturated NaHCO3 dried over anhydrous Na2SO4 concentrated

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

Procedure: A mixture of 5-bromo-2-iodobenzaldehyde (14.9) (1.0 g, 3.2 mmol) and PTSA (0.1 g) in ethanol was stirred under reflux for 18 hrs and concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with saturated NaHCO3, dried over anhydrous Na2SO4 and concentrated to give 4-bromo-2-(diethoxymethyl)-1-iodobenzene (14.10) that was directly used in next reaction without further purification. under reflux for 18 hrs concentrated under reduced pressure The residue was dissolved in ethyl acetate washed with saturated NaHCO3 dried over anhydrous Na2SO4 concentrated

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

Procedure: Prepared according to the procedure described in Example 1, Step 4, using the following starting materials: 5-bromo-2-iodo-benzaldehyde and [4-methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester. Prepared

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

Procedure: Prepared according to the procedure described in Example 1, Step 4, using the following starting materials: 5-bromo-2-iodo-benzaldehyde and [4-methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester. Prepared

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

Procedure: To 5-bromo-2-iodo-benzaldehyde (5.0 g, 16.1 mmol) in MeOH (20 mL) was added ethylamine (2M in MeOH; 16 mL, 24.0 mmol), followed by acetic acid (1.0 mL, 17.8 mmol), and the mixture was stirred at room temperature for 30 minutes. Sodium cyanoborohydride (2.0 g, 31.8 mmol) was then added over 5 minutes, and the reaction was stirred at room temperature over the weekend. The mixture was concentrated and partitioned between EtOAc and saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography (0-5% MeOH in CH2Cl2) to give the title compound. the reaction was stirred at room temperature over the weekend The mixture was concentrated partitioned between EtOAc and saturated aqueous NaHCO3 The aqueous layer was extracted with EtOAc the combined organic layers were dried over MgSO4 filtered concentrated The residue was purified by silica gel chromatography (0-5% MeOH in CH2Cl2)

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

Procedure: To 5-bromo-2-iodo-benzaldehyde (5.0 g, 16.1 mmol) in MeOH (20 mL) was added ethylamine (2M in MeOH; 16 mL, 24.0 mmol), followed by acetic acid (1.0 mL, 17.8 mmol), and the mixture was stirred at room temperature for 30 minutes. Sodium cyanoborohydride (2.0 g, 31.8 mmol) was then added over 5 minutes, and the reaction was stirred at room temperature over the weekend. The mixture was concentrated and partitioned between EtOAc and saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography (0-5% MeOH in CH2Cl2) to give the title compound. the reaction was stirred at room temperature over the weekend The mixture was concentrated partitioned between EtOAc and saturated aqueous NaHCO3 The aqueous layer was extracted with EtOAc the combined organic layers were dried over MgSO4 filtered concentrated The residue was purified by silica gel chromatography (0-5% MeOH in CH2Cl2)

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

Procedure: To 5-bromo-2-iodobenzonitrile (7.4 g, 24.2 mmol) in THF (40 mL) at −78° C. was added diisobutylaluminium hydride (1 M in hexanes; 24.2 mL, 24.2 mmol) over 5 minutes, and the reaction was allowed to warm to room temperature and monitored by analytical tlc. After stirring overnight at room temperature, starting material was still present, so the mixture was cooled to 0° C. and additional diisobutylaluminium hydride (1 M in hexanes; 10.0 mL, 10.0 mmol) was added. After stirring for 2 hours at room temperature, no starting material was seen by analytical tlc, so the mixture was carefully quenched with freshly saturated aqueous Na2SO4 and diluted with EtOAc. The mixture was stirred vigorously for 1 hour and then filtered through Celite. The filtrate was concentrated, and the resulting oil solidified on standing. The solid was stirred vigorously in CH2Cl2 and 1N aqueous HCl, and the aqueous layer was separated and extracted with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound. was cooled to 0° C. After stirring for 2 hours at room temperature was carefully quenched with freshly saturated aqueous Na2SO4 diluted with EtOAc The mixture was stirred vigorously for 1 hour filtered through Celite The filtrate was concentrated The solid was stirred vigorously in CH2Cl2 1N aqueous HCl, and the aqueous layer was separated extracted with CH2Cl2 The combined organic layers were dried over MgSO4 filtered concentrated