1-Bromo-3-chloropropane → (2R)-1-(3-chloropropyl)-2-methylpyrrolidine

Temperature

80 °C

To a solution of (R)-2-methylpyrrolidine (18.0 g) and 1-bromo-3-chloropropane (100.0 g) in acetone (360 mL), 5M aqueous sodium hydroxide (50 mL) was added dropwise in an ice bath and stirred at 80° C. for 4 hours. The reaction mixture was cooled to room temperature and extracted with diethyl ether. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=4/1 to 1/1) and silica gel column chromatography (eluting solvent: chloroform/methanol=9/1) to give the titled compound (17.8 g, 52%) as a yellow oil.

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionextracted with diethyl ether
3. washThe organic layer was washed with brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customthe resulting residue was purified by NH-type silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=4/1 to 1/1) and silica gel column chromatography (eluting solvent: chloroform/methanol=9/1)

ORD record

ord-019b5170528240f99b37e33d5c100aa3

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609847B2