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

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 (3 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%).

1. custom(reaction becomes dark red)
2. customThe reaction was quenched with NaHSO3 and water (pH 2.5)
3. extractionthen extracted with EtOAc (4×30 mL)
4. dry with materialAfter drying (Na2SO4)
5. filtrationthe solution was filtered
6. concentrationconcentrated to a yellow oil which
7. customwas chromatographed on Silica gel
8. customto provide a yellow oil
9. customabove yielded 5 g, 67%)

ORD record

ord-7ae447ae520f4aedae2b49c4ebb6fbb9

Source dataset

uspto-grants-2002_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06410550B1