1,3-Dibromopropane → HCID 23079680, compound

Temperature

50 °C

Tert-butyl 3-oxo-piperazinecarboxylate (1.5 g, 7.5 mmol) was dissolved in tetrahydrofuran (15 mL), and the solution was mixed with sodium bis(trimethylsilyl)amide (1.0 mol/L, 15 mL, 15 mmol) added dropwise with stirring under ice-cooling. After ten minutes, 1,3-dibromopropane (3.0 mL, 30 mmol) was added dropwise. The reaction mixture was heated to 50° C., was stirred for three hours, was poured onto water and was extracted with ethyl acetate. The organic layer was washed with brine, was dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (hexane:ethyl acetate=1:2) to thereby remove residual raw materials, and the solvent was distilled off. The residue was dissolved in dimethylformamide (12 mL), and the solution was mixed with pyrrolidine (1.6 mL, 19 mmol) and potassium carbonate (0.57 g, 4.1 mmol), followed by stirring at 80° C. for eight hours. The reaction mixture was diluted with water and was extracted with ethyl acetate. The organic layer was mixed with diluted hydrochloric acid (1.0 mol/L, 30 mL), and the organic layer and the aqueous layer were separated. The aqueous layer was adjusted to be basic with an aqueous sodium hydroxide solution (2.0 mol/L) and was extracted with ethyl acetate. The organic layer was washed with brine, was dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel chromatography (chloroform:7.0 mol/L ammonia methanol solution=30:1) and thereby yielded tert-butyl 3-oxo-4-(3-pyrrolidin-1-yl-propyl)piperazinecarboxylate (0.16 g, 6.8%).

1. additionadded dropwise
2. temperaturecooling
3. waitAfter ten minutes
4. stirringwas stirred for three hours
5. additionwas poured onto water
6. extractionwas extracted with ethyl acetate
7. washThe organic layer was washed with brine
8. dry with materialwas dried over anhydrous sodium sulfate
9. distillationthe solvent was distilled off
10. customThe residue was purified by silica gel chromatography (hexane:ethyl acetate=1:2)
11. customto thereby remove residual raw materials
12. distillationthe solvent was distilled off
13. dissolutionThe residue was dissolved in dimethylformamide (12 mL)
14. stirringby stirring at 80° C. for eight hours
15. extractionwas extracted with ethyl acetate
16. additionThe organic layer was mixed with diluted hydrochloric acid (1.0 mol/L, 30 mL)
17. customthe organic layer and the aqueous layer were separated
18. extractionwas extracted with ethyl acetate
19. washThe organic layer was washed with brine
20. dry with materialwas dried over anhydrous sodium sulfate
21. distillationthe solvent was distilled off
22. customThe residue was purified by silica gel chromatography (chloroform:7.0 mol/L ammonia methanol solution=30:1)

ORD record

ord-3575cb64b32145a08294c8596b080945

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07524852B2