Thionyl Chloride → 1-Benzyl-2-(chloromethyl)pyrrolidine

Into a 5,000 ml 3-necked roundbottom flask, was placed a solution of (1-benzylpyrrolidin-2-yl)methanol (250. g, 1.30 mol) in chloroform (2,500 ml). This was followed by the dropwise addition of a solution of thionyl chloride (232. g, 1.95 mol) in chloroform (500 ml), while maintaining the internal temperature at room temperature (60 minute addition time). The resulting solution was heated to reflux for 2 hours. After cooling to ambient temperature, the mixture was concentrated, and the resulting residue was dissolved in 3,000 ml of ethyl acetate. Adjustment of the pH to 7 was accomplished by the addition of triethylamine. The resulting mixture was filtered and the filtrate was concentrated and the residue was purified by flash column chromatography (ethylacetate/petroleum ether gradient) to afford 1-benzyl-2-(chloromethyl)pyrrolidine.

1. customInto a 5,000 ml 3-necked roundbottom flask, was placed
2. addition(60 minute addition time)
3. temperatureThe resulting solution was heated
4. temperatureto reflux for 2 hours
5. temperatureAfter cooling to ambient temperature
6. concentrationthe mixture was concentrated
7. dissolutionthe resulting residue was dissolved in 3,000 ml of ethyl acetate
8. additionAdjustment of the pH to 7 was accomplished by the addition of triethylamine
9. filtrationThe resulting mixture was filtered
10. concentrationthe filtrate was concentrated
11. customthe residue was purified by flash column chromatography (ethylacetate/petroleum ether gradient)

ORD record

ord-d21cc5e537544f998cf5b95260a136fc

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08455477B2