1,2-Dichloroethane → ethyl 6-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate

Participants

Reaction Steps

To a suspension of 6-bromo-2-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid (18.5 g, 42.4 mmol), EDC (10.58 g, 55 2 mmol), and 1-hydroxybenzotriazole hydrate (8.45 g, 55.2 mmol) in THF/CH2Cl2 (5/1) (480 mL) was added ammonium hydroxide (9.91 mL, 76 mmol) and it turned into a thick light yellow suspension and it was stirred at room temperature over the weekend. CAUTION: A mild exotherm was observed. The reaction mixture warmed up to 31° C. If reaction is done on larger scale, consider cooling or slow addition of one of the reagents. The reaction mixture was concentrated and then titurated with 500 ml water (sonicate for 2 minutes), then filtered through a medium porosity glass frit. The solids were washed with water and dried in a nitrogen stream to give 15.1 g ethyl 6-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate. MS (ESI) m/e−=363/365, m/e+=365/367 [1Br isotope pattern]. 1H NMR (DMSO-d6) δ ppm 10.97 (s, 1H), 8.10 (b, 1H), 7.74 (d, 1H, J=1.8), 7.68 (d, 1H, J=1.5), 7.44 (b, 1H), 4.16-4.06 (m, 2H), 3.04 (dd, 1H, J=16.2, 5.0), 2.95-2.83 (m, 2H), 2.75-2.68 (m, 1H), 2.67-2.58 (m, 1H), 2.18-2.12 (m, 1H), 1.87-1.79 (m, 1H), 1.21 (t, 3H, J=7.0).

Provenance & Evidence