Hydrochloric Acid → 1-(4-Bromobenzoyl)piperazine hydrochloride

温度

20 °C

With ice cooling, 100 mL (1.2 mol) of concentrated hydrochloric acid was added in portions to a solution of 100.0 g (1.16 mol) of piperazine in water (200 mL)-methanol (300 ml) and the mixture was stirred for 30 minutes. To the resulting solution was added dropwise a solution of 127.4 g (0.58 mol) of 4-bromobenzoyl chloride in tetrahydrofuran (300 mL) over about 40 minutes, and the mixture was stirred for 30 minutes. The reaction mixture was concentrated under reduced pressure to remove tetrahydrofuran. To the residue was added water (2 L) and the mixture was stirred for 2 hours at 70° C. At this temperature, insoluble materials were filtered off and the residue was washed with hot water (20 mL). The filtrate and the washing were combined. After cooling to about 20° C., 74.4 g (1.86 mol) of sodium hydroxide was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Isopropanol (400 mL) was added to the residue and the mixture was concentrated under reduced pressure. Isopropanol (1 L) was added again to the residue. The mixture was stirred at 50° C. to obtain a homogenous solution. Over about 20 minutes, 50 mL (0.60 mol) of concentrated hydrochloric acid was added dropwise to the resulting solution. After stirring for 10 minutes at 50° C., the mixture was cooled to room temperature, and stirred in an ice bath. The precipitates were collected by filtration and washed with isopropanol, whereby 140.1 g of 1-(4-bromobenzoyl)piperazine hydrochloride was obtained as colorless fine needles (yield: 79%).

1. stirringthe mixture was stirred for 30 minutes
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. customto remove tetrahydrofuran
4. additionTo the residue was added water (2 L)
5. stirringthe mixture was stirred for 2 hours at 70° C
6. filtrationAt this temperature, insoluble materials were filtered off
7. washthe residue was washed with hot water (20 mL)
8. extractionthe mixture was extracted with ethyl acetate
9. washThe organic layer was washed with saturated saline
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationconcentrated under reduced pressure
12. additionIsopropanol (400 mL) was added to the residue
13. concentrationthe mixture was concentrated under reduced pressure
14. additionIsopropanol (1 L) was added again to the residue
15. stirringThe mixture was stirred at 50° C.
16. customto obtain a homogenous solution
17. waitOver about 20 minutes
18. stirringAfter stirring for 10 minutes at 50° C.
19. temperaturethe mixture was cooled to room temperature
20. stirringstirred in an ice bath
21. filtrationThe precipitates were collected by filtration
22. washwashed with isopropanol

ORDレコード

ord-7f6725b2db254555b2332955f5ab3065

出典データセット

uspto-grants-2004_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06787653B2