Diethyl Ether → m-Chloroamphetamine

Temperature

60 °C

To a solution of 3-chlorobenzylmagnesium chloride (0.1 mol) in anhydrous ether (100 mL) (prepared from 3-chlorobenzyl chloride (16.1 g, 0.1 mol) and magnesium turnings (2.4 g, 0.1 mol) in anhydrous ether (100 mL)) was added anhydrous acetonitrile (4.1 g, 0.1 mol) dropwise at room temperature. When the reaction mixture was stirred at 60° C. for 3 hours, it was cooled to 0° C. followed by addition of THF (50 mL). Lithium aluminum hydride (4.2 g, 0.1 mol) was then added cautiously into the above reaction mixture and it was heated to reflux temperature for 3 hours. Ice-water was added to quench the reaction. After partitioning between ether and H2O, the separated organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo. Flash column chromatography separation (silica gel, 180 g, 5% methanol in DCM) then yielded the title compound as yellowish oil (1.9 g, 11%). MS: 170.1 (M+H+).

1. temperatureit was cooled to 0° C.
2. temperaturewas heated
3. temperatureto reflux temperature for 3 hours
4. customto quench
5. customthe reaction
6. customAfter partitioning between ether and H2O
7. washthe separated organic layer was washed with brine
8. customdried over anhy
9. filtrationNa2SO4, filtered
10. concentrationconcentrated in vacuo
11. customFlash column chromatography separation (silica gel, 180 g, 5% methanol in DCM)

ORD record

ord-66c53230c8d3475cb1997a70938f618d

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133158B2