Heptane → 1,3-Bis[4-[4-(3,4,5-trimethoxyphenyl)benzoyl]-1-piperazinyl]propane

In toluene (200 mL)-methanol (50 mL) were dissolved 50.0 g (86.5 mmol) of 1,3-bis[4-(4-bromobenzoyl)-1-piperazinyl] propane and 42.16 g (199 mmol) of 3,4,5-trimethoxyphenylboronic acid. The mixture was degassed with nitrogen. A solution of 9.35 g (173 mmol) of sodium methoxide in methanol (150 mL) was added in portions, then a solution of 9.35 g (173 mmol) of sodium methoxide in methanol (150 mL) and a solution of 970 mg (4.32 mmol) of palladium(II) acetate in toluene (150 mL) were added dropwise simultaneously over about 1 hour. After stirring for 1 hour at room temperature, 9.2 g of activated carbon was added and the mixture was stirred under hydrogen for 3 hours at room temperature. Insoluble materials were filtered off by filtration through Celite and the residue was washed with methanol-toluene (1:1,3×75 mL). The filtrate and the washings were combined and concentrated under reduced pressure, then water-isopropanol (5:1, 750 mL) was added. After stirring for 30 minutes at room temperature, precipitates were collected by filtration and washed with water-isopropanol (5:1, 3×100 mL) to obtain 65.6 g of crude crystals. To a suspension of the crude crystals (65.6 g) in methanol-tetrahydrofuran (1:2, 350 mL) stirred at 70° C. was added 3.3 g of activated carbon, and the mixture was stirred for 1.5 hours. Insoluble materials were filtered off at the same temperature and the residue was washed with hot methanol-tetrahydrofuran (1:2, 2×130 mL). The filtrate and the washings were combined and stirred at 70° C. to obtain a homogeneous solution, then heptane (390 mL) was added over about 1 hour. The mixture was stirred for 30 minutes at room temperature and for 1 hour in an ice bath. Precipitates were collected by filtration and washed with tetrahydrofuran-heptane (1:5, 3×130 mL) to obtain 59.48 g of 1,3-bis[4-[4-(3,4,5-trimethoxyphenyl)benzoyl]-1-piperazinyl] propane as a colorless crystalline powder (yield: 92%).mp: 192.0 to 193.5° C.

1. customThe mixture was degassed with nitrogen
2. addition9.2 g of activated carbon was added
3. stirringthe mixture was stirred under hydrogen for 3 hours at room temperature
4. filtrationInsoluble materials were filtered off by filtration through Celite
5. washthe residue was washed with methanol-toluene (1:1,3×75 mL)
6. concentrationconcentrated under reduced pressure
7. additionwater-isopropanol (5:1, 750 mL) was added
8. stirringAfter stirring for 30 minutes at room temperature
9. customprecipitates
10. filtrationwere collected by filtration
11. washwashed with water-isopropanol (5:1, 3×100 mL)
12. customto obtain 65.6 g of crude crystals
13. stirringstirred at 70° C.
14. additionwas added 3.3 g of activated carbon
15. stirringthe mixture was stirred for 1.5 hours
16. filtrationInsoluble materials were filtered off at the same temperature
17. washthe residue was washed with hot methanol-tetrahydrofuran (1:2, 2×130 mL)
18. stirringstirred at 70° C.
19. customto obtain a homogeneous solution
20. stirringThe mixture was stirred for 30 minutes at room temperature and for 1 hour in an ice bath
21. customPrecipitates
22. filtrationwere collected by filtration
23. washwashed with tetrahydrofuran-heptane (1:5, 3×130 mL)

ORD record

ord-477e203b55b14d01a8b5eb85b93e28d5

Source dataset

uspto-grants-2004_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06787653B2