Iodine → HCID 68211900, compound

A mixture of 1-bromo-2-(bromomethyl)benzene (4.40 g, 17.60 mmol), magnesium (0.984 g, 40.5 mmol), and I2 (2.2 mg, 8.80 μmol) in Et2O (87 mL) was heated to reflux under argon until the reaction initiated (indicated by decolorization of I2) and then stirred at room temperature for 2 hours. After this time, the reaction mixture was added to a solution of tert-butyl 4-acetylpiperidine-1-carboxylate (2 g, 8.80 mmol) in Et2O (1.2 mL) and then stirred for 19 hours. At the conclusion of this period, the reaction mixture was quenched with aqueous NH4Cl (saturated, 20 mL) and extracted with EtOAc (3×25 mL). The combined organic layers were washed with H2O (3×15 mL) and brine (15 mL). The resulted organic layer was separated, dried (Na2SO4), filtered, and concentrated to yield a residue. The residue was purified by column chromatography (silica gel, hexanes/EtOAc gradient 0 to 60% EtOAc) to afford Compound 11A as a white semi-solid (1.14 g, 31% yield).

1. temperaturewas heated
2. temperatureto reflux under argon until the reaction
3. stirringstirred for 19 hours
4. customAt the conclusion of this period, the reaction mixture was quenched with aqueous NH4Cl (saturated, 20 mL)
5. extractionextracted with EtOAc (3×25 mL)
6. washThe combined organic layers were washed with H2O (3×15 mL) and brine (15 mL)
7. customThe resulted organic layer was separated
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customto yield a residue
12. customThe residue was purified by column chromatography (silica gel, hexanes/EtOAc gradient 0 to 60% EtOAc)

ORD record

ord-cedccc482a8b4851b08d2423538c3b05

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08729084B2