Potassium Iodide → 2,2,2-trifluoro-1-(7-iodo-4,5-dihydro-1H-1,5-methanobenzo[d]azepin-3(2H)-yl)ethanone

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Reaction Steps

1-(4-Amino-10-aza-tricyclo[6.3.1.02,7]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoro-ethanone (500 mg, 1.85 mmol) was dissolved in H2O (5 mL) and concentrated H2SO4 solution (0.5 mL) then cooled to 0° C. and treated with a solution of sodium nitrite (NaNO2) (140 mg, 2.04 mmol) in H2O (2 mL) dropwise. Potassium iodide (460 mg, 2.78 mmol) in 1N H2SO4 solution (0.5 mL) was added over 10 minutes (reaction becomes dark red). The resulting solution was warmed to room temperature and stirred 18 hours. The reaction was quenched with NaHSO3 and water (pH 2.5) then extracted with EtOAc (4×30 mL). After drying (Na2SO4), the solution was filtered and concentrated to a yellow oil which was chromatographed on Silica gel to provide a yellow oil. (260 mg, 37%). (TLC 30% EtOAc/hexanes Rf 0.70). (A 5.4 g scale performed as above yielded 5 g, 67%).

Provenance & Evidence