N-(1-benzylpiperidin-4-yl)-2,2,2-trifluoroacetamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Using 4 g of 10% palladium-on-carbon (50% hydrous) as a catalyst, 11.431 g (39.927 mM) of N-(1-benzyl-piperidin-4-yl)trifluoroacetamide was hydrogenated in 100 ml of methanol at room temperature and atmospheric pressure until the starting compound had disappeared (i.e. for 2 hours). The catalyst in the reaction mixture was filtered off with the aid of celite and washed with methanol. The filtrate and washes were pooled and the solvent was distilled off under reduced pressure to provide crude N-(piperidin-4-yl)trifluoroacetamide. This crude product was not purified but used as it was in the next reaction. To a solution of the crude N-(piperidin-4-yl)trifluoroacetamide and 6.68 ml (47.9 mM) of triethylamine in tetrahydrofuran (50 ml)-methanol (20 ml) was added 9.59 g (43.9 mM) of di-tert-butyl dicarbonate dropwise at room temperature and the mixture was stirred at the prevailing temperature overnight. The solvent was then distilled off under reduced pressure and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1) to provide the title compound. (i.e. for 2 hours) The catalyst in the reaction mixture was filtered off with the aid of celite washed with methanol the solvent was distilled off under reduced pressure

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 500 mL, three-necked round-bottomed flask under nitrogen was charged with 4 g of 10% Palladium on Carbon, and 100 mL of methanol. The suspension was cooled to 5° C. and 10 g of ammonium formate was added in one batch (evolution of gas was observed). A solution of 10 g (35 mmol) of the 4-trifluoroacetamido-1-benzylpiperidine in 100 mL of methanol was then added dropwise gradually. The resulting reaction mixture was refluxed for 2.5 hr. and then at room temperature overnight. The catalyst was filtered off through Celite under a blanket of nitrogen and washed with ethanol. The filtrate was concentrated under reduced pressure to give 6.9 g (quantitative yield) of a light yellow solid of the title compound. The resulting reaction mixture was refluxed for 2.5 hr at room temperature overnight The catalyst was filtered off through Celite under a blanket of nitrogen washed with ethanol The filtrate was concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 92 g of 1-benzyl 4-trifluoromethylcarbonylamino piperidine (X) and 9 g of wet 10% palladium on charcoal in 1000 ml of methanol is left under agitation for 8 days in a hydrogen atmosphere at room temperature. Then it is filtered, the filtrate is evaporated and the residue chromatographed on a silica column (M.P.L.C.). By eluting with pure methanol, 44 g of the expected product are obtained. Then it is filtered the filtrate is evaporated the residue chromatographed on a silica column (M.P.L.C.) By eluting with pure methanol, 44 g of the expected product are obtained

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-(1-benzyl-4-piperidinyl)-2,2,2-trifluoroacetamide (1.0 g, 3.49 mmol) was added to a suspension of 60%-sodium hydride (147 mg, 3.67 mmol) in tetrahydrofuran (20 ml) at room temperature and stirred for 30 minutes. Then, methyl iodide (0.239 ml, 3.84 mmol) was added thereto and stirred for 5 hours. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=100/1) to obtain N-(1-benzyl-4-piperidinyl)-2,2,2-trifluoro-N-methylacetamide (731 mg, 70%). stirred for 5 hours extracted with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate distilled under reduced pressure to remove the solvent the resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=100/1)