Iodine → (3R)-3-Amino-6-(2,3-dichlorophenyl)azepan-2-one

To a slurry of 1-bromo-2,3-dichlorobenzene (1.46 g, 6.46 mmol) in diethyl ether (10 mL) was added magnesium (0.157 g, 6.46 mmol) and a crystal of iodine. This mixture was refluxed for 3 h, and then cooled to room temperature. A solution of benzyl (2R,5E)-2-[bis(tert-butoxycarbonyl)amino]-6-nitrohex-5-enoate (0.50 g, 1.08 mmol) in diethyl ether (10 mL) was cooled to 0° C., and 2.0 mL of the Grignard solution prepared above was added. After 1 and 2 h, respectively, 2.0 and 1.0 mL of the Grignard solution was added. The reaction was quenched with a saturated aqueous solution of ammonium chloride, the phases separated and the organic phase washed with saturated aqueous sodium potassium tartrate and brine. The combined organics were dried over magnesium sulfate, filtered and concentrated to give a residue that was purified by silica gel chromatography (0%→-3% methanol/dichloromethane) to give the title compound (0.52 g). MS 411.0 (M+1-2Boc).

1. temperatureThis mixture was refluxed for 3 h
2. custom2.0 mL of the Grignard solution prepared
3. additionabove was added
4. additionAfter 1 and 2 h, respectively, 2.0 and 1.0 mL of the Grignard solution was added
5. customThe reaction was quenched with a saturated aqueous solution of ammonium chloride
6. customthe phases separated
7. washthe organic phase washed with saturated aqueous sodium potassium tartrate and brine
8. dry with materialThe combined organics were dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a residue that
12. customwas purified by silica gel chromatography (0%→-3% methanol/dichloromethane)

ORD record

ord-ddcf34ddfbd144f69a74f792e76089f7

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07452903B2