1-benzyl-2-(chloromethyl)pyrrolidine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 3,000 ml 3-necked roundbottom flask, was placed a solution of 1-benzyl-2-(chloromethyl)pyrrolidine (150. g, 714 mmol) in N,N-dimethylformamide (1,500 ml). This was followed by the addition of a solution of NaCN (54.2 g, 834 mmol) in water (300 ml). The resulting solution was heated to reflux for 2 hours. After cooling to ambient temperature, the solution was dissolved in 6,000 ml of water. The resulting solution was extracted with ethyl acetate (3×3,000 ml) and the combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography (ethylacetate/petroleum ether gradient) to afford 2-(1-benzylpyrrolidin-2-yl)acetonitrile. Into a 3,000 ml 3-necked roundbottom flask, was placed The resulting solution was heated to reflux for 2 hours The resulting solution was extracted with ethyl acetate (3×3,000 ml) the combined organic layers were dried over sodium sulfate filtered concentrated The residue was purified by flash column chromatography (ethylacetate/petroleum ether gradient)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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. Into a 5,000 ml 3-necked roundbottom flask, was placed (60 minute addition time) The resulting solution was heated to reflux for 2 hours After cooling to ambient temperature the mixture was concentrated 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 the filtrate was concentrated the residue was purified by flash column chromatography (ethylacetate/petroleum ether gradient)