1-Bromo-3-chloropropane → 1-(3-chloropropyl)pyrrolidine Hydrochloride

Temperature

42.5 °C

A solution of 1-bromo-3-chloropropane (99.5 kg) in toluene (237 kg) was heated to 40-45° C. To this solution was added pyrrolidine (94.5 kg) over 1.5 hours, maintaining the temperature at 40-45° C. A line wash of toluene (37 kg) was applied and the reaction maintained at 40-45° C. for a further four hours. The reaction mixture was cooled to 20-25° C. and washed with water (211 kg). Further water (138 kg) was added and the pH adjusted to 8.8-9.0 by the addition of 34% w/w hydrochloric acid (4.7 kg). The aqueous phase was separated and discarded. To the organic phase was added 34% w/w hydrochloric acid (61 kg) until the pH was 0.5-1.0. The aqueous was separated and concentrated under vacuum, maintaining the temperature <50° C. until the toluene content was <0.1%, giving an aqueous solution of 1-(3-chloropropyl)pyrrolidine hydrochloride 129.1 kg at 71.5% w/w, 79.9%

1. washA line wash of toluene (37 kg)
2. temperaturethe reaction maintained at 40-45° C. for a further four hours
3. temperatureThe reaction mixture was cooled to 20-25° C.
4. washwashed with water (211 kg)
5. additionFurther water (138 kg) was added
6. additionthe pH adjusted to 8.8-9.0 by the addition of 34% w/w hydrochloric acid (4.7 kg)
7. customThe aqueous phase was separated
8. additionTo the organic phase was added 34% w/w hydrochloric acid (61 kg) until the pH was 0.5-1.0
9. customThe aqueous was separated
10. concentrationconcentrated under vacuum
11. temperaturemaintaining the temperature <50° C. until the toluene content

ORD record

ord-b53167d96b7a497faf8ac7b4e7903468

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07851623B2