methyl 3-bromo-5-iodobenzoate

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

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

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

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

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

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

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

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To methyl 5-bromo-3-iodobenzoate (Step A above) (5.01 g, 0.015 mole) in anhydrous methylene chloride (100 mL) at -78° C., was added dropwise minutes, diisobutylaluminum hydride (5.50 mL, 0.03 mole). The mixture was stirred for 1 hour then allowed to warm to 0° C. The reaction solution was poured into 600 mL, chilled 3N HCl and extracted 3× with methylene chloride (150 mL). The organic layers were combined, dried over MgSO4 and concentrated under vacuum to yield 5-bromo-3-iodobenzyl alcohol (4.54 g) as a white solid. MP=110-112° C. MS and NMR were consistent with the desired structure. The reaction solution was poured into 600 mL extracted 3× with methylene chloride (150 mL) dried over MgSO4 concentrated under vacuum

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

Procedure: Methanol (40 mL) was added to a 250 mL round bottom flask followed by 60 mL of a solution saturated with anhydrous hydrochloric acid. 3-bromo-5-iodobenzoic acid (Aldrich)(5.02 g, 0.015 mole) was then added and the reaction mixture was stirred at room temperature for 6 hours. The reaction mixture was poured into chilled saturated NaHCO3 solution (700 mL). The mixture was extracted 3× with methylene chloride (100 mL). The organic layers were combined, dried over MgSO4 and concentrated under vacuum to yield methyl-5-bromo-3-iodobenzoate (5.08 g) as a pink solid. MP=55-57° C. MS and NMR were consistent with the desired structure. The reaction mixture was poured The mixture was extracted 3× with methylene chloride (100 mL) dried over MgSO4 concentrated under vacuum

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

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

Procedure: To a suspension of 3-bromo-5-iodobenzoic acid (993 g, 3.04 mol) in methanol (6.0 L) was added hydrochloric acid (37%; 20.0 mL, 244 mmol). The mixture was heated to 70° C. After 72 h, the mixture was cooled to ambient temperature. Dichloromethane (2.5 L) was added and the mixture was partially concentrated. The suspension was filtered and the filtered cake was washed with cold methanol to give the title compound as a white solid (846 g). the mixture was cooled to ambient temperature the mixture was partially concentrated The suspension was filtered the filtered cake was washed with cold methanol