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

Temperature

60 °C

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)+.

1. temperatureto cool to ambient temperature
2. extractionwas extracted with EtOAc (75 mL)
3. washThe organic layer was washed with brine (50 mL)
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe product was purified by silica gel chromatography (40 g column)
8. washeluting with a gradient of 1-5% MeOH in DCM

ORD record

ord-005f8826ce6a42e4ba332320411aa925

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365579B2