1-[(4-fluorophenyl)methyl]piperidine

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

実験手順: To a stirred solution of 4-fluorobenzaldehyde (500 mg, 4.0 mmol) in DCE (3 ml) at RT was added piperidine (309 mg, 3.6 mmol) followed by AcOH (242 mg, 4.0 mmol). The solution was stirred at RT for 2 h, and then STAB (1.3 g, 6.05 mmol) was added in one portion. The resulting mixture was stirred at RT overnight and then quenched with saturated NaHCO3 (10 ml). The organic layer was separated, dried (Na2SO4), filtered and concentrated at reduced pressure. Purification by silica flash column chromatography (eluting with DCM/MeOH/NH3 90:10:1) provided the title compound as colourless oil (650 mg, 95%). STAB (1.3 g, 6.05 mmol) was added in one portion The resulting mixture was stirred at RT overnight quenched with saturated NaHCO3 (10 ml) The organic layer was separated dried (Na2SO4) filtered concentrated at reduced pressure Purification by silica flash column chromatography (eluting with DCM/MeOH/NH3 90:10:1)

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

実験手順: To a stirred solution of 4-fluorobenzaldehyde (500 mg, 4.0 mmol) in DCE (3 ml) at RT was added piperidine (309 mg, 3.6 mmol) followed by AcOH (242 mg, 4.0 mmol). The solution was stirred at RT for 2 h, and then STAB (1.3 g, 6.05 mmol) was added in one portion. The resulting mixture was stirred at RT overnight and then quenched with saturated NaHCO3 (10 ml). The organic layer was separated, dried (Na2SO4), filtered and concentrated at reduced pressure. Purification by silica flash column chromatography (eluting with DCM/MeOH/NH3 90:10:1) provided the title compound as colourless oil (650 mg, 95%). STAB (1.3 g, 6.05 mmol) was added in one portion The resulting mixture was stirred at RT overnight quenched with saturated NaHCO3 (10 ml) The organic layer was separated dried (Na2SO4) filtered concentrated at reduced pressure Purification by silica flash column chromatography (eluting with DCM/MeOH/NH3 90:10:1)

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

実験手順: To a cooled (0° C.) solution of 1-(4-fluorobenzyl)piperidine (5.0 g, 24.1 mmol) in anhydrous THF (100 mL) was added lithium bis(trimethylsilyl)amide (1.0 M in THF, 53 mL, 53 mmol) dropwise, and the solution was stirred for one half hour. The solution was treated with methyl benzene sulfinate (5.65 g, 36.1 mmol) in anhydrous THF (3 mL) dropwise. After 30 minutes at 0° C., the resultant mixture was quenched with water and partitioned between 10% KHSO4 and CHCl3, the layers separated and the aqueous extracted several more times with CHCl3. The organic extract was dried with Na2SO4, filtered, and concentrated under vacuum to afford 1-(4-fluorobenzyl)-3-(phenylsulfinyl)piperidin-2-one as a waxy solid that was taken on to the next step. ES MS M+1=332 the resultant mixture was quenched with water partitioned between 10% KHSO4 and CHCl3 the layers separated The organic extract was dried with Na2SO4 filtered concentrated under vacuum

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a cooled (−20° C.) solution of 1-(4-fluorobenzyl)piperidine (17 g, 82 mmol) in anhydrous THF (200 mL) was added LiHMDS (1.0M in THF, 180 mL, 180 mmol) over a period of 15 min. The reaction mixture was stirred for 30 min at −20° C., then methyl phenylsulfinate (15 g, 98 mmol) was added over a period of 5 min. After being stirred at −20° C. for 1 hour, the reaction was quenched by the addition of water (100 mL). EtOAc (200 mL) was added and the organic layer was separated and washed with water (3×100 mL) and brine. The organic layer was dried over Mg2SO4, filtered, concentrated under vacuum. The crude product was used without purification in the next step. After being stirred at −20° C. for 1 hour the reaction was quenched by the addition of water (100 mL) EtOAc (200 mL) was added the organic layer was separated washed with water (3×100 mL) and brine The organic layer was dried over Mg2SO4 filtered concentrated under vacuum The crude product was used without purification in the next step