Iodine → 3-iodo-7-fluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one

Temperature

-15 °C

7-fluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (411 mg, 2.3 mmol) (Step A) dissolved in a mixture of 7.9 mL of dry methylene chloride and 1.0 mL of dry tetrahydrofuran was treated with 1.62 mL (1.18 g, 11.6 mmol, 5 eq) of triethylamine and the resulting solution cooled to -15° C. Iodotrimethylsilane (0.66 mL, 932 mg, 4.7 mmol, 2 eq) was added followed by 1.183 g of iodine (4.7 mmol, 2 eq) added in small portions over 5 minutes. The mixture was warmed to room temperature over 5 minutes at which time 15 mL of methylene chloride was added followed by 20 mL of 10% aqueous sodium sulfite. The layers were separated and the organic layer washed with 10% sodium sulfite (3×20 mL). The aqueous layer was further extracted with 20 mL of methylene chloride. The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated to dryness under vacuum. The crude product was chromatographed on silica gel, eluting with methylene chloride/methanol (99:1) to afford 511 mg (1.68 mmol, 73%) of the product. 1H NMR (300 MHz, CDCl3): 2.70 (m,3H), 2.93 (m,1H), 4.62 (t,9 Hz,1H), 6.95 (m,3H), 7.86 (br s,1H). FAB-MS: calculated for C10H9FINO 305; found 306 (M+H,100%).

1. additionadded in small portions over 5 minutes
2. additionwas added
3. customThe layers were separated
4. washthe organic layer washed with 10% sodium sulfite (3×20 mL)
5. extractionThe aqueous layer was further extracted with 20 mL of methylene chloride
6. washThe combined extracts were washed with brine
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated to dryness under vacuum
10. customThe crude product was chromatographed on silica gel
11. washeluting with methylene chloride/methanol (99:1)

ORD record

ord-e9ab89a7affd4faab496a36dc49a283f

Source dataset

uspto-grants-1993_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05206235