Triethylamine → Benzyl 3-[methoxy(methyl)carbamoyl]piperidine-1-carboxylate

Benzyl 3-(hydroxymethyl)piperidine-1-carboxylate (2.0 g, 8.0 mmol) in dichloromethane (50 mL) was stirred with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (5.1 g, 12 mmol) at room temperature for 2.5 hours. After addition of a mixture (1/1(v/v)) of saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium thiosulfate, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in t-butanol (25 mL), mixed with sodium dihydrogen phosphate (2.89 g, 24.1 mmol), water (25 mL) and 2-methyl-2-butene (25 mL, 241 mmol), then stirred with sodium chlorite (3.62 g, 40.1 mmol) at 0° C. for 1 hour and then stirred at room temperature for 1 hour. After addition of saturated aqueous sodium thiosulfate, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (60 mL) and mixed with N,O-dimethylhydroxylamine hydrochloride (1.02 g, 10.4 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (4.0 g, 10.4 mmol) and then stirred with triethylamine (1.5 mL, 10 mmol) at room temperature for 2.5 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1→1/1 (v/v)) to give the title compound as a pale yellow oil (1.44 mg, yield 59% (three steps)).

1. extractionthe reaction mixture was extracted with ethyl acetate
2. dry with materialthe organic layer was dried over anhydrous sodium sulfate
3. concentrationconcentrated under reduced pressure
4. dissolutionThe resulting residue was dissolved in t-butanol (25 mL)
5. extractionthe reaction mixture was extracted with ethyl acetate
6. dry with materialthe organic layer was dried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. dissolutionThe resulting residue was dissolved in N,N-dimethylformamide (60 mL)
9. extractionthe reaction mixture was extracted with ethyl acetate
10. dry with materialthe organic layer was dried over anhydrous sodium sulfate
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1→1/1 (v/v))

ORD-Eintrag

ord-457adb304dc3495e99a27d0bff519dc5

Quelldatensatz

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09216999B2