4,4'-Difluorobenzophenone → HCID 22989269, compound

25 g of 4,4′-difluorobenzophenone was dissolved in ethanol-tetrahydrofuran (180 ml-60 ml); 2.16 g of sodium borohydride was added under ice cooling conditions, followed by stirring at room temperature for 30 minutes. The mixture was concentrated under reduced pressure; the residue was diluted with ice water and extracted with ethyl acetate; the extract was washed with saline and dried with magnesium sulfate. The dry product was concentrated under reduced pressure; the oily substance obtained was dissolved in 800 ml of toluene; 11.6 g of 4-hydroxypiperidine and 23.7 g of p-toluenesulfonic acid monohydrate were added, followed by thermal refluxing for 2 hours. After cooling, the mixture was concentrated under reduced pressure; ice water and 130 ml of a 1 N aqueous solution of sodium hydroxide were added, followed by extraction with ethyl acetate; the extract was washed with saline and dried with magnesium sulfate. The dry product was concentrated under reduced pressure; the oily substance obtained (34.5 g) was dissolved in 100 ml of N,N-dimethylformamide; 16.3 g of N-(3-bromopropyl)phthalimide and 10.5 g of potassium carbonate were added, followed by stirring at room temperature for 20 hours. Ice water was added to the reaction mixture, followed by extraction with ethyl acetate; the extract was washed with saline and dried with magnesium sulfate. The dry product was concentrated under reduced pressure; the residue was subjected to silica gel column chromatography and eluted with hexane-ethyl acetate (1:2). The desired fraction was collected to yield 20.5 g of N-[3-[4-[bis(4-fluorophenyl)methoxy]piperidino]propyl]-phthalimide as an oily substance. 20.5 g of this oily substance was dissolved in 150 ml of ethanol; 2.02 ml of hydrazine monohydrate was added, followed by thermal refluxing for 3 hours. After cooling, the mixture was concentrated under reduced pressure; ethanol was added to the residue; the crystal precipitated was collected, dissolved in 40 ml of a 1 N aqueous solution of sodium hydroxide and extracted with ethyl acetate-tetrahydrofuran (2:1); the extract was washed with saline and dried with sodium sulfate. The dry product was concentrated under reduced pressure to yield 12.07 g of the title compound as an oily substance.

1. concentrationThe mixture was concentrated under reduced pressure
2. additionthe residue was diluted with ice water
3. extractionextracted with ethyl acetate
4. washthe extract was washed with saline
5. dry with materialdried with magnesium sulfate
6. concentrationThe dry product was concentrated under reduced pressure
7. customthe oily substance obtained
8. customrefluxing for 2 hours
9. temperatureAfter cooling
10. concentrationthe mixture was concentrated under reduced pressure
11. additionice water and 130 ml of a 1 N aqueous solution of sodium hydroxide were added
12. extractionfollowed by extraction with ethyl acetate
13. washthe extract was washed with saline
14. dry with materialdried with magnesium sulfate
15. concentrationThe dry product was concentrated under reduced pressure
16. customthe oily substance obtained (34.5 g)
17. stirringby stirring at room temperature for 20 hours
18. extractionfollowed by extraction with ethyl acetate
19. washthe extract was washed with saline
20. dry with materialdried with magnesium sulfate
21. concentrationThe dry product was concentrated under reduced pressure
22. washeluted with hexane-ethyl acetate (1:2)
23. customThe desired fraction was collected

ORD record

ord-7bae5daf946f460ab13dd3ffe7e3bae6

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06248740B1