Methylamine → [(1R)-1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethyl]methylamine

To a magnetically stirred solution of (1R)-1-(4-bromophenyl)-2-(1-pyrrolidinyl)ethanol (29.43 g, 109 mmol) in CH2Cl2 (300 mL) at 0° C. was added triethylamine (55 mL, 394 mmol). Methanesulfonylchloride (30 mL, 388 mmol) was then added dropwise. The resulting mixture was warmed to room temperature, stirred for 5 h, and then quenched by the addition of H2O (200 mL). The layers were separated and the organic phase was washed with saturated aqueous NaHCO3 and brine, dried over MgSO4, filtered and concentrated under reduced pressure to give an orange oil. The crude oil was taken up in CH2Cl2 (300 mL) and methylamine (33 wt % in EtOH, 135 mL, 1.08 mol) was added at room temperature. The resulting mixture was stirred overnight at room temperature. The mixture was concentrated under reduced pressure and re-dissolved in CH2Cl2. The crude mixture was washed with saturated aqueous NaHCO3 and brine, dried over MgSO4, filtered and concentrated under reduced pressure to give (1R)-1-(4-bromophenyl)-N-methyl-2-(1-pyrrolidinyl)ethanamine as a viscous red/orange oil (25.4 g, 90 mmol, 82% yield).

1. customquenched by the addition of H2O (200 mL)
2. customThe layers were separated
3. washthe organic phase was washed with saturated aqueous NaHCO3 and brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto give an orange oil
8. stirringThe resulting mixture was stirred overnight at room temperature
9. concentrationThe mixture was concentrated under reduced pressure
10. dissolutionre-dissolved in CH2Cl2
11. washThe crude mixture was washed with saturated aqueous NaHCO3 and brine
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure

ORD record

ord-ddfa6bb4d91243969424122bc3a3c7dd

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07749998B2