Potassium Carbonate → 5-Bromo-1-(3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)isoquinoline

Participants

Reaction Conditions

Reaction Steps

A dried round bottomed flask was charged with 5-bromo-2-(phenylcarbonyl)-1,2-dihydro-1-isoquinolinecarbonitrile (D10; 687 mg, 2.03 mmol) and dry, nitrogen purged N,N-dimethylformamide (DMF) (15 ml). The solution was cooled to −10° C. with stirring in an ice/methanol bath at which temperature the flask was evacuated. The flask was closed from the vacuum and allowed to warm to room temperature before the vacuum was re-introduced and the vessel then filled with nitrogen. (3-Bromopropoxy)-tert-butyldimethylsilane (available from Aldrich; 0.563 ml, 2.43 mmol) was added, the vessel purged with nitrogen three times and the solution cooled again to −10° C. To the solution was added sodium hydride (97 mg, 2.43 mmol) as a single portion. The mixture was held at −10° C. for 5 minutes before being allowed to warm to room temperature and stirred under nitrogen for 5 hours. To the mixture was added potassium carbonate (560 mg, 4.05 mmol). The slurry was warmed to 80° C. for 3 hours before being filtered through a plug of celite (ethyl acetate eluent). The organic layers were further diluted with ethyl acetate and partitioned with water (×3) then brine. The aqueous fractions were discarded and the organic layers passed through a hydrophobic frit before being concentrated in vacuo to give a tan oil. The oil was dissolved in DCM and purified by flash column chromatography on silica using 0% to 20% ethyl acetate in cyclohexane gradient elution. The relevant fractions were pooled and concentrated in vacuo to give the title compound as a yellow semi-solid (0.64 g).

Provenance & Evidence