Propanoic acid, 3-iodo- → 7-(2-Carboxy-ethoxy)-8-iodo-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

Into a 100 ml flask, the product of step (d) (1.28 g, 3.54 mmol) dissolved in DMF (15 ml) was added. The solution was cooled to 0° C. and NaH (354 mg, 8.86 mmol) was added, followed by 3-iodopropionic acid (1.06 g 5.31 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 1.5 hours, after which time it was heated to 70° C. for an additional 1 hour. The reaction mixture was cooled to room temperature and quenched by the addition of water (100 ml) and 2M NaOH (15 ml). The aqueous mixture was washed with EtOAc (2×), acidified with 2M HCl to pH 2, and extracted with EtOAc (3×). The combined EtOAc extracts were washed with brine, dried over Na2SO4, and solvent evaporated in vacuo to give crude product. Purification by silica-gel chromatography (gradient elution: 0 to 60% EtOAc in hexanes) gave the sub-title compound as an off-white solid (580 mg) and recovered starting material (515 mg). MS: ESI (positive): 434 (M+H).

Provenance & Evidence