Triethylamine → 6-(Dibenzylamino)-8-fluoroisoquinolin-1(2H)-one

Participants

Reaction Steps

A solution of ethyl chloroformate (0.320 mL, 3.35 mmol) in acetone (5 mL) was added dropwise to a suspension of 19C (1.013 g, 2.80 mmol) in a mixture of acetone (30 mL) and triethylamine (0.90 mL, 6.4 mmol) at 0° C. The reaction mixture was stirred for 45 min and then a solution of sodium azide (0.350 g, 5.4 mmol) in water (8 mL) was added dropwise over 1 h. After an additional 1 h, the reaction was warmed to rt, poured into ice water, and the solid was isolated by filtration and washed with water (Do not allow the solid to dry out). (Caution: this acyl azide intermediate is potentially explosive and should be handled in small quantities behind a safety shield.) The solid was dissolved in DCM, dried (MgSO4), filtered, and the volume reduced to ˜2 mL with a stream of nitrogen. Diphenyl ether (2 mL) was added, and the crude acyl azide solution was used directly. The acyl azide solution was added slowly dropwise via addition funnel to a refluxing mixture of diphenyl ether (8.12 g) and tributylamine (2 mL), internal temperature ˜230° C. A flow of dry nitrogen was maintained through the reaction vessel to a bubbler during the reaction. Reflux was continued for an additional 1 h, after which time the majority of the solvent was removed in vacuo. The residue was cooled to room temperature and hexanes was added. The solid was collected by filtration and washed with hexanes to give 19D (0.830 g, 83%) as an off-white solid. LC-MS m/z: 359.4 (M+H)+.

Provenance & Evidence