Uses
2-(2-Iodophenyl)-N,N-dimethylacetamide is an intermediate in the synthesis of 3''-Hydroxy-4''-methoxydiclofenac (H946710), a derivative of Diclofenac (Sodium Salt: D436450). Diclofenac is the first non-steroidal anti-inflammatory drug (NSAID) that is derived from phenylacetic acid. Diclofenac, like other NSAIDs, primarily works by targeting the cyclo-oxygenase pathway in the arachidonic acid cascade, reducing the formation of inflammation mediators in the body.
Preparation
synthesis of 2-(2-Iodo)phenyl-N,N-dimethylacetamide: A round-bottom flask was charged with phenyl acetic acid (0.867 g, 3.32 mmol), dimethylammonium hydrochloride (0.245 g, 3 mmol), and HBTU (1.23 g, 3.3 mmol). Acetonitrile (15 mL) was added, followed by DIEA (1.62 mL, 9.3 mmol), and the resulting solution was stirred under argon for 15 h. The reaction mixture was concentrated to a syrup that was redissolved in EtOAc (100 mL). The organic layer was washed with 1 N HCl (30 mL) followed by 10% NaHCO3 (30 mL). The organic layer was dried (anhydrous Na2SO4), filtered, and concentrated. Purification of the crude product by flash chromatography using a gradient of EtOAc in hexanes (5-40%) afforded a colorless oil that solidified to a white solid under high vacuum (0.82 g, 94%).
1H NMR (CDCl3): δ 7.83 (dd, J ) 8.1, 1.3 Hz, 1H), 7.31 (ddd, J ) 7.5, 7.4, 0.8 Hz, 1H), 7.26 (dd, J ) 7.5, 1.7 Hz, 1H), 6.94 (ddd, J ) 7.5, 7.4, 1.7 Hz, 1H), 3.80 (s, 2H), 3.04 (s, 3H), 3.01 (s, 3H). 13C NMR (CDCl3): δ 170.13, 139.32, 139.29, 138.72, 129.85, 128.48, 101.09, 45.77, 37.66, 35.65.
