Hydrochloric Acid → 1-{[(9H-fluoren-9-yl)methoxy]carbonyl}-4-methylpiperidine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(tert-butoxycarbonyl)-4-methylpiperidine-3-carboxylic acid (1.50 g, 6.17 mmol, Example #13, Step G) in 1,4-dioxane (10 mL) was added aqueous HCl (4N in 1,4-dioxane (4.62 mL, 18.5 mmol). The reaction mixture was heated at about 60° C. for about 16 h before being allowed to cool to ambient temperature. To the mixture was added NaHCO3 (2.07 g, 24.7 mmol) and water (10.0 mL) followed by (9H-fluoren-9-yl)methyl 2,5-dioxopyrrolidin-1-yl carbonate (4.16 g, 12.3 mmol). The reaction was stirred at about 25° C. for about 16 h. The reaction was acidified to about pH 1 with aqueous 1N HCl and was extracted with EtOAc (75 mL). The organic layer was washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The product was purified by silica gel chromatography (40 g column) eluting with a gradient of 1-5% MeOH in DCM to give 1-(((9H-fluoren-9-yl)methoxy)carbonyl)-4-methylpiperidine-3-carboxylic acid (0.72 g, 31%) as a clear oil: LC/MS (Table 2, Method a) Rt=2.44 min; MS m/z: 366 (M+H)+.

Provenance & Evidence