Triethylamine → 5-fluoro-3-iodo-1H-indole-2-carboxylic acid (3-oxo-propyl)-amide

Participants

Reaction Steps

To a solution of oxalyl chloride (3.68 g, 30 mmol) in anhydrous CH2Cl2 (50 mL) at −40° C. is added DMSO (4.52 g, 57.9 mmol) drop-wise. The mixture is stirred at this temperature for 5 minutes. 5-Fluoro-3-iodo-1H-indole-2-carboxylic acid (3-hydroxy-propyl)-amide, prepared as in reference 12, (6.99 g, 19.3 mmol) is dissolved in CH2Cl2 (800 mL) with small amount of DMSO (10 mL) and added to the above-mentioned solution at −40° C. The reaction is stirred for additional 30 minutes before adding Et3N (11.7 g, 0.116 mol). The mixture is allowed to warm to room temperature and quenched with H2O (1 L). The organic layer is separated and washed with citric acid (10%, 500 mL), saturated NaHCO3 (500 mL) and brine (500 mL). It is dried with Na2SO4 to give 5-fluoro-3-iodo-1H-indole-2-carboxylic acid (3-oxo-propyl)-amide; 1H NMR (DMSO-d6) δ 2.75 (dt, 2H, J1=1.2 Hz, J2=6.0 Hz), 3.61 (q, 2H, J=5.2 Hz), 7.06-7.17 (m, 2H), 7.45 (dd, 1H, J1=4.8 Hz, J2=8.8 Hz), 8.11 (t, 1H, J=5.6 Hz), 9.74 (t, 1H, 1.2 Hz), 12.10 (s, 1H); m/z [M++1] 361.0.

Provenance & Evidence