Dichloromethane → 4-[3-(2-Fluoro-pyridin-3-yl)-indole-1-sulfonyl]-benzoic acid methyl ester

Participants

Reaction Steps

Reflux a mixture of 4-(3-iodo-indole-1-sulfonyl)-benzoic acid methyl ester (1.33 g, 3.01 mmol, 1 equiv), 2-fluoropyridine-3-boronic acid (Frontier Scientific®; 0.47 g, 3.3 mmol, 1.1 equiv), sodium carbonate (2M in H2O; 3.0 mL, 6.0 mmol, 2.0 equiv), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (62 mg, 0.080 mmol, 0.025 equiv) in THF (15 mL) under N2 for 2 h (reaction mixture turned very dark when heated). Rotary evaporate the reaction mixture. Dissolve the resultant residue in Et2O (15 mL) and wash with H2O (5 mL). Back-extract the aqueous layer is with Et2O (5 mL). Dry the combined organic layers with (anhydr Na2SO4), and rotary evaporate (40° C.) giving the crude 4-[3-(2-fluoro-pyridin-3-yl)-indole-1-sulfonyl]-benzoic acid methyl ester as a brown foam. Dissolve this material in THF (10 mL) and add 5M aq NaOH (2 mL). After 18 h, add H2O (25 mL) and Et2O (25 mL). Separate the aqueous layer and extract the organic layer with H2O (25 mL). Combine the aqueous layers and wash with Et2O (25 mL). Acidify this aqueous layer with 1M aq HCl (8 mL) to pH 5 causing much precipitation. Extract this mixture with CHCl3 (1×50 mL, 2×25 mL). Dry the combined organic layers (anhydr Na2SO4) and rotary evaporate (40° C.) yielding 673 mg (56.3%) of 4-[3-(2-fluoro-pyridin-3-yl)-indole-1-sulfonyl]-benzoic acid as a brown powder. MS (m/e): 396.94 (M+1); 394.99 (M−1).

Provenance & Evidence