Potassium Phosphate, Tribasic → Potassium Phosphate, Tribasic

Participants

Reaction Conditions

Reaction Steps

A 0.25M solution of 6-bromo-2,3-dihydrobenzofuran was prepared in dioxane. A 0.30M 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 1.00M solution of K3PO4 was prepared in water. In a vial was added 400 uL of the 0.30M dioxane solution of 6-bromo-2,3-dihydrobenzofuran (100 umol, 1.00 eq). 400 uL of the 0.25M 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 1.00M 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