Potassium Phosphate, Tribasic → Potassium Phosphate, Tribasic

Participants

Reaction Conditions

Reaction Steps

A 0.25 M solution of 6-bromo-2,3-dihydrobenzofuran was prepared in dioxane. A 0.30 M solution of methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate was also prepared in dioxane. Lastly, a 1.00 M solution of K3PO4 was prepared in water. In a vial was added 400 uL of the 0.30 M dioxane solution of 6-bromo-2,3-dihydrobenzofuran (100 umol, 1.00 eq). 400 uL of the 0.25 M dioxane solution of methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (120 umol, 1.20 eq) was then added followed by the addition of 200 uL of the 1.00 M aqueous solution of K3PO4 (200 umol, 2.00 eq). Under nitrogen atmosphere was added (1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (3.9 mg, 6.0 umol, 0.06 eq). The vial was caped and shook for 2 hours at 120° C. The reaction was filtered and concentrated by Speedvac. The residue was washed with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (1 mL, 3×). The organic layer was collected and dried over anhydrous sodium sulfate, filtered, and concentrated to give crude methyl 6-chloro-5-(2,3-dihydrobenzofuran-6-yl)-1H-indole-3-carboxylate. To the crude intermediate was added anhydrous tetrahydrofuran (1.5 mL) followed by Me3SiOK (128 mg, 1000 umol, 10.0 eq). The vial was capped and shaken at 80° C. for 16 hours. The reaction was concentrated by Speedvac and the residue was purified by preparative HPLC to provide the title compound. MS (ES+) 314 (M+H)+. Retention time: 2.56 min. Column: Agella Venusil ASB dC18 150×21.2 mm, 5 μm. Modifier: TFA 0.225%. Gradient: 66% H2O/34% MeCN linear to 36% H2O/64% MeCN over 10.0 min., HOLD at 100% MeCN to 1.0 min. Flow: 30.0 mL/min.

Provenance & Evidence