Ethyl Acetate → 1-Methyl-3-(1-methylethyl)-5-(4-morpholinyl)-1H-indole-7-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

Methyl 5-bromo-3-isopropyl-1-methyl-1H-indole-7-carboxylate (502 mg, 1.62 mmol), methanesulfinic acid, Sodium salt (811 mg, 7.9 mmol) and copper(I) iodide 1.51 g, 7.9 mmol) were suspended in N-Methyl-2-pyrrolidone (5 mL) in a sealed vial and the mixture was stirred at 150° C. for 10 hours. The suspension was cooled down, EtOAc was added and insoluble materials were removed by filtration. The filtrate was extracted with EtOAc and DCM and the combined organics were washed with brine, dried over MgSO4, filtered and the solvent evaporated. The residue was purified using normal phase chromatography Hexanes/EtOAc (gradient 0 to 100% EtOAc). Solids that crashed out were filtered, air-dried for 15 min and dried in vacuum-oven overnight to give 1-methyl-3-(1-methylethyl)-5-(4-morpholinyl)-1H-indole-7-carboxylic acid (125 mg, 62.2% yield). EtOAc was added along with some hexanes, it was sonicated, the solids that crashed out were filtered, air-dried for 15 min and dried in vacuum-oven overnight to give methyl 3-isopropyl-1-methyl-5-(methylsulfonyl)-1H-indole-7-carboxylate (198 mg, 39%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.31 (s, 3H) 1.33 (s, 3H) 3.22-3.28 (m, 4H) 3.82 (s, 3H) 3.96 (s, 3H) 7.43 (s, 1H) 7.99 (d, J=1.77 Hz, 1H) 8.32 (d, J=1.77 Hz, 1H). MS (ES) [M+H]+ 310.1.

Provenance & Evidence