N-Hydroxyphthalimide → Phthalimide

(S)-3-Hydroxypiperidine hydrochloride was dissolved in distilled water (2.5 ml), sodium hydrogencarbonate (889 mg) was added to the solution, a solution (2.5 ml) of 4-nitrobenzyl chloroformate (836 mg) in acetone was slowly was added to the mixture at room temperature, and the resulting mixture was stirred for 2 hours. Ethyl acetate and distilled water were added to the reaction mixture, and the layers were separated. The organic layer was dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane to hexane:ethyl acetate=1:2) to obtain a protected compound (971 mg). (2) The compound obtained in (1) mentioned above (971 mg) was dissolved in tetrahydrofuran, N-hydroxyphthalimide (848 mg) and triphenylphosphine (1.36 g) were added to the solution. Diisopropyl azodicarboxylate (1.02 ml) was added to the reaction mixture under ice cooling, and then the resulting mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane to hexane:ethyl acetate=1:2) to obtain a phthalimide compound (1.52 g). (3) The compound obtained in (2) mentioned above (1.52 g) was dissolved in ethanol (10 ml) and chloroform (10 ml), hydrazine monohydrate (638 μl) was added to the solution under reflux by heating, and the resulting mixture was stirred for 1.5 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane to hexane:ethyl acetate=1:2), then a 4 mol/L solution of hydrochloric acid in dioxane (866 μl) was added to the purified residue, and the resulting mixture was concentrated under reduced pressure to obtain the title compound (825 mg).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. customthe resulting residue was purified by silica gel column chromatography (hexane to hexane:ethyl acetate=1:2)

ORD record

ord-6eebaea126a546729fa4f9444b30e60d

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139609B2