Sodium Carbonate → Methyl-7-chloro-3-cyclohexyl-2-(4-methoxyphenyl)-1H-indole-6-carboxylate

Participants

Reaction Conditions

Reaction Steps

To 572.0 mgs (1.54 mmol) of Methyl-2-bromo-7-chloro-3-cyclohexyl-1H-indole-6-carboxylate in 8 mL of toluene and 8 mL of ethanol was added 2 equivalents of LiCl (3.08 mmol, 130.6 mgs), 2.5 equivalents of Na2CO3 (3.85 mmol, 408.1 mgs) in 4 mL of water, and 1.5 equivalents of para-methoxyphenyl boronic acid (2.31 mmol, 351.0 mgs). To this mixture was then added 0.1 equivalents of PdCl2(PPh3)2 (150.0 μmol, 105.3 mgs), and the mixture was degassed then flushed with N2 (×3). The reaction mixture was heated to 70° C. overnight. After 18 hours, the mixture was cooled to room temperature, concentrated to near dryness then extracted with ethyl acetate. The crude product was purified using automated flash chromatography (Biotage Horizon™, gradient elution, 0 to 40% Ethyl Acetate/Hexane) to give 502.0 mgs (82%) of Methyl-7-chloro-3-cyclohexyl-2-(4-methoxyphenyl)-1H-indole-6-carboxylate as an ivory colored solid. The LC/MS data was obtained on a Shimadzu analytical LC/Micromass Platform LC (ESI+) at 220 nm using the following set of conditions: Phenomenex 10 μm C18, 4.6×30 mm column, with a gradient of 0-100% B (B=90% HPLC grade methanol/0.1% trifluoroacetic acid/10% HPLC grade water), (A=90% HPLC grade water/0.1% trifluoroacetic acid/10% HPLC grade methanol), in 2 minutes with a 1 minute hold at a rate of 5 mL/minute.

Provenance & Evidence