Hydrogen Bromide → (3S)-(+)-1-Benzyl-3-aminopyrrolidine

(S)-1-Benzyl-3-(p-toluenesulfonylamino)pyrrolidine hydrochloride (40.0 g), phenol (12.0 g) and 30% hydrogen bromide in acetic acid (200 mL) were combined and heated in a sealed flask at 105° C. to 125° C. for a period of 55 minutes. The resulting red solution was concentrated under vacuum to remove excess acetic acid and hydrogen bromide and the thick oil dissolved in water (500 mL) and toluene (150 mL). The layers were separated and the aqueous layer extracted with toluene (50 mL) and diethyl ether (30 mL) and treated with 28% ammonium hydroxide (11 mL) to give a pH of 8.5. This solution was extracted with toluene (25 mL) and all of the organic extracts discarded. The remaining aqueous layer was treated with 50% NaOH (145 mL) and extracted with toluene (3×50 mL). The combined toluene extracts were concentrated to an oil (19.2 g) which was distilled under vacuum (bp 104°-106° C. at 2.5 mm Hg) to give (S)-3-amino-1-benzylpyrrolidine, 5, (18.2 g, 94%) as a colorless oil: [α]25 =+11.2°.

1. temperatureheated in a sealed flask at 105° C. to 125° C. for a period of 55 minutes
2. concentrationThe resulting red solution was concentrated under vacuum
3. customto remove excess acetic acid and hydrogen bromide
4. dissolutionthe thick oil dissolved in water (500 mL)
5. customThe layers were separated
6. extractionthe aqueous layer extracted with toluene (50 mL) and diethyl ether (30 mL)
7. additiontreated with 28% ammonium hydroxide (11 mL)
8. customto give a pH of 8.5
9. extractionThis solution was extracted with toluene (25 mL)
10. additionThe remaining aqueous layer was treated with 50% NaOH (145 mL)
11. extractionextracted with toluene (3×50 mL)
12. concentrationThe combined toluene extracts were concentrated to an oil (19.2 g) which
13. distillationwas distilled under vacuum (bp 104°-106° C. at 2.5 mm Hg)

ORD record

ord-efbd98dc4769432d9b4a64a1a7adceb3

Source dataset

uspto-grants-1993_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05250704