benzyl (2R,5S)-5-hydroxy-2-methylpiperidine-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzyl (2R,5S)-5-hydroxy-2-methylpiperidine-1-carboxylate (6.8 g, 27.3 mmol) was dissolved in DCM (100 mL) containing crushed molecular sieves. N-methylmorpholine N-oxide (4.15 g, 35.5 mmol) and tetrapropylammonium perruthenate (0.48 g, 1.36 mmol) were added, and the reaction was stirred at room temperature for 1.5 hours. The mixture was filtered through a celite pad and concentrated. The residue was purified by silica gel chromatography (0-30% ethyl acetate/hexanes, linear gradient) to afford benzyl (2R)-2-methyl-5-oxopiperidine-1-carboxylate. MS ESI calc'd. for C14H17NO3 [M+H]+ 248. found 248. containing crushed molecular sieves The mixture was filtered through a celite pad concentrated The residue was purified by silica gel chromatography (0-30% ethyl acetate/hexanes, linear gradient)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzyl (2R,5S)-5-hydroxy-2-methylpiperidine-1-carboxylate (6.8 g, 27.3 mmol) was dissolved in DCM (100 mL) containing crushed molecular sieves. N-methylmorpholine N-oxide (4.15 g, 35.5 mmol) and tetrapropylammonium perruthenate (0.48 g, 1.36 mmol) were added, and the reaction was stirred at room temperature for 1.5 hours. The mixture was filtered through a celite pad and concentrated. The residue was purified by silica gel chromatography (0-30% ethyl acetate/hexanes, linear gradient) to afford benzyl (2R)-2-methyl-5-oxopiperidine-1-carboxylate. MS ESI calc'd. for C14H17NO3 [M+H]+ 248. found 248. containing crushed molecular sieves The mixture was filtered through a celite pad concentrated The residue was purified by silica gel chromatography (0-30% ethyl acetate/hexanes, linear gradient)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a THF (909 ml) solution of benzyl (2R,5S)-5-hydroxy-2-methylpiperidine-1-carboxylate (34 g, 136 mmol), 4-(dimethylamino) phenyldiphenylphosphine (58.3 g, 191 mmol), and 4-nitrobenzoic acid (29.6 g, 177 mmol) was added, under N2, DEAD (30.0 ml, 191 mmol) dropwise at −15 to −25° C. over 20 min. The reaction was allowed to warm to RT overnight. The reaction was concentrated in vacuo, removing most THF, then diluted with Et2O (500 mL). The mixture was cooled at 0° C. and washed with 1 N HCl (5×200 mL). The combined aqueous phases were back-extracted twice with Et2O. The combined organic phases were subsequently washed twice more with 1 N HCl. The organics were dried over MgSO4, filtered, and concentrated. The crude material was purified by silica gel gradient chromatography (0-40% ethyl acetate in hexanes), providing the titled compound as a light yellow oil which slowly solidified. LRMS m/z (M+H) 399.3 found, 399.1 required. The reaction was concentrated in vacuo removing most THF diluted with Et2O (500 mL) The mixture was cooled at 0° C. washed with 1 N HCl (5×200 mL) The combined aqueous phases were back-extracted twice with Et2O The combined organic phases were subsequently washed twice more with 1 N HCl The organics were dried over MgSO4 filtered concentrated The crude material was purified by silica gel gradient chromatography (0-40% ethyl acetate in hexanes)