Carbon Dioxide → (1-[(tert-Butyldimethylsilyloxy)prop-1-yl]-1H-indol-4-yl)oxoacetic Acid Methyl Ester

Participants

Reaction Steps

Add tert-butyl lithium (88.1 ml, 149.8 mmol, 1.7 M in hexane) to a solution of 4-Bromo-1-[3-(tert-butyldimethyl-silyloxy)propyl]-1H-indole (22.0 g, 59.92 mmol) in anhydrous tetrahydrofuran (100 ml) at −78° C. Stir the reaction at −78° C. for 20 min. Transfer the mixture into a solution of dimethyl oxalate (24.8 g, 209.72 mmol) in tetrahydrofuran (400 ml) at −40° C. via a dry-ice cooled cannula. Upon complete addition, stir the reaction at −78° C. for 15 minutes and slowly warm to room temperature. Quench the reaction with saturated aqueous ammonium chloride and extract into ethyl acetate. Combine the organic layers, dry over magnesium sulfate, and concentrate under reduced pressure. Purification by flash chromatography and eluting with ethyl acetate:hexane gradient (100% hexane to 15% ethyl acetate:hexane over 90 minutes) gives the title compound (16.89 g, 75%), as a light brown oil. ESMS (M++1): 376.2 m/z.

Provenance & Evidence