Sodium Bicarbonate → tert-Butyl-3-{1-[tert-butyl(dimethyl)silyl]-1H-indol-3-yl}-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate

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Reaction Conditions

Reaction Steps

To 4.8 g (15.5 mmol) 3-bromo-1-(tert-butyl-dimethyl-silanyl)-1H-indole in 60 mL THF at −78° C. is added 19.1 mL (32.5 mmol) of a 1.7M solution of t-BuLi/pentane in drops over 10 min. After stirring at −78° C. for 30 min, 3.48 g (15.5 mmol) 3-oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester in 20 mL THF is added via a cannula over 5 min. After stirring at 23° C. for 3 h, the reaction mixture is poured into sat. aqueous NaHCO3, and extracted with 2×50 mL EtOAc. The combined organics are washed with 1×100 mL H2O, 1×100 mL brine, dried over MgSO4, filtered and evaporated to an orange oil. Flash chromatography on SiO2 gel, eluting with CH2Cl2/EtOAc (80/1 to 20/1), gives 3.74 g (8.2 mmol, a 53% yield) of the title compound as an off-white wax. MS (ES) m/z 457 (MH)+.

Provenance & Evidence