4,4'-Difluorobenzophenone → HCID 22989269, compound

Participants

Reaction Steps

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.

Provenance & Evidence