2,2-diphenylacetaldehyde

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:

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: Nipecotic acid (300 mg, 2.38 mmol), diphenylacetaldehyde (1.26 mL, 7.13 mmol), sodium cyanoborohydride (448 mg, 7.13 mmol), and HOAc (204 uL, 3.57 mmol) were dissolved in MeOH (20 mL) and stirred at ambient temperature overnight. The solution was concentrated under reduced pressure, take up in ether and 1N NaOH, extract with ether (3×), acidify the aqueous layer with 1N HCl, and extract with EtOAc (3×). The EtOAc layers were dried (MgSO4) and concentrated to give the title compound without further purification. The solution was concentrated under reduced pressure 1N NaOH, extract with ether (3×) extract with EtOAc (3×) The EtOAc layers were dried (MgSO4) concentrated

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

実験手順: Nipecotic acid (300 mg, 2.38 mmol), diphenylacetaldehyde (1.26 mL, 7.13 mmol), sodium cyanoborohydride (448 mg, 7.13 mmol), and HOAc (204 uL, 3.57 mmol) were dissolved in MeOH (20 mL) and stirred at ambient temperature overnight. The solution was concentrated under reduced pressure, take up in ether and 1N NaOH, extract with ether (3×), acidify the aqueous layer with 1N HCl, and extract with EtOAc (3×). The EtOAc layers were dried (MgSO4) and concentrated to give the title compound without further purification. The solution was concentrated under reduced pressure 1N NaOH, extract with ether (3×) extract with EtOAc (3×) The EtOAc layers were dried (MgSO4) concentrated

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

実験手順: Reductive amination of 4-(aminomethyl)-1-(4-chlorobenzyl)piperidine (120 mg) with 2,2-diphenylacetaldehyde (0.66 equiv.) and polymer-supported borohydride in methanol at 25° C. for 16 h, followed by general workup and column chromatography (SiO2) afforded 1-(4-chlorobenzyl)-4-{N-(2,2-diphenylethyl)aminomethyl}piperidine (70 mg, 49%): The purity was determined by RPLC (98%).

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

実験手順: Reductive amination of 4-(aminomethyl)-1-(4-chlorobenzyl)piperidine (120 mg) with 2,2-diphenylacetaldehyde (0.66 equiv.) and polymer-supported borohydride in methanol at 25° C. for 16 h, followed by general workup and column chromatography (SiO2) afforded 1-(4-chlorobenzyl)-4-{N-(2,2-diphenylethyl)aminomethyl}piperidine (70 mg, 49%): The purity was determined by RPLC (98%).

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

実験手順: To a mixture of ethylmagnesium bromide (5.7 ml; 3.0M/L in ether solution) and THF (40 ml) was added dropwise a solution of the compound prepared in reference example 30 (3.0 g) in THF (20 ml) over a 10 min period. The mixture was stirred for 2 h at room temperature. To the mixture was added a solution of diphenylacetaldehyde (2.94 g) in THF (10 ml). The mixture was stirred for 2 h. After quenched by addition of ammonium chloride, the mixture was extracted with ether. The extract was washed with water and a saturated aqueous solution of sodium chloride, successively, dried over anhydrous magnesium sulfate, and evaporated. To a solution of the residue in ether (50 ml) was added manganese (IV) oxide (2.7 g) at room temperature. The mixture was stirred for 2 h. The mixture was filtrated, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=7:1) to give the title compound (2.41 g) having the following physical data. was added dropwise a solution of the compound The mixture was stirred for 2 h After quenched by addition of ammonium chloride the mixture was extracted with ether The extract was washed with water a saturated aqueous solution of sodium chloride, successively, dried over anhydrous magnesium sulfate evaporated To a solution of the residue in ether (50 ml) was added manganese (IV) oxide (2.7 g) at room temperature The mixture was stirred for 2 h The mixture was filtrated evaporated The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=7:1)

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

実験手順: To a mixture of ethylmagnesium bromide (5.7 ml; 3.0M/L in ether solution) and THF (40 ml) was added dropwise a solution of the compound prepared in reference example 30 (3.0 g) in THF (20 ml) over a 10 min period. The mixture was stirred for 2 h at room temperature. To the mixture was added a solution of diphenylacetaldehyde (2.94 g) in THF (10 ml). The mixture was stirred for 2 h. After quenched by addition of ammonium chloride, the mixture was extracted with ether. The extract was washed with water and a saturated aqueous solution of sodium chloride, successively, dried over anhydrous magnesium sulfate, and evaporated. To a solution of the residue in ether (50 ml) was added manganese (IV) oxide (2.7 g) at room temperature. The mixture was stirred for 2 h. The mixture was filtrated, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=7:1) to give the title compound (2.41 g) having the following physical data. was added dropwise a solution of the compound The mixture was stirred for 2 h After quenched by addition of ammonium chloride the mixture was extracted with ether The extract was washed with water a saturated aqueous solution of sodium chloride, successively, dried over anhydrous magnesium sulfate evaporated To a solution of the residue in ether (50 ml) was added manganese (IV) oxide (2.7 g) at room temperature The mixture was stirred for 2 h The mixture was filtrated evaporated The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=7:1)

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

実験手順: 200 mg (0.468 mmol) of (2R*,4S*)-2-benzyl-N-(4-quinolylmethyl)-N-trifluoroacetyl-4-piperidinamine are reacted in analogy to Example 11 with 88 mg (1.4 mmol) of sodium cyanoborohydride, 115 mg (1.4 mmol) of sodium acetate, 134 μl (2.34 mmol) of acetic acid and 335 μl (1.87 mmol) of diphenylacetaldehyde with the product. TLC: methylene chloride/methanol/conc. ammonia (2000:50:1) Rf =0.50, FD-MS: M+ =607.