Trifluoroacetic acid → tert-Butyl 4-hydroxy-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate

Temperatur

60 °C

To a solution of 1-tert-butyl 4-methyl 4-(2-((tert-butoxycarbonyl)amino)-1-hydroxyethyl)piperidine-1,4-dicarboxylate (4000 mg, 9.94 mmol) in DCM (100 mL) was added TFA (23 mL, 298 mmol) at 0° C. and the resulting solution was stirred for 2 h. After removing the volatiles, it was put on high vacuum briefly to remove excess TFA, and the residue was dissolved in MeOH (100 mL), and potassium carbonate (13.7 g, 99 mmol) was added. The reaction mixture was heated at 60° C. for 2 h. After cooling to room temperature, aqueous NaHCO3 (50 mL) was added to the reaction mixture. (BOC)2O (6.51 g, 29.8 mmol) was added, and the reaction mixture was stirred overnight. The reaction mixture was extracted with DCM, dried with MgSO4, and concentrated to give the crude product, which was purified by column chromatography (0-20% MeOH/DCM, monitor at 210 nm) to afford the title compound. LC/MS: [(M+1)]+=271

1. customAfter removing the volatiles, it
2. customto remove excess TFA
3. dissolutionthe residue was dissolved in MeOH (100 mL)
4. temperatureAfter cooling to room temperature
5. stirringthe reaction mixture was stirred overnight
6. extractionThe reaction mixture was extracted with DCM
7. dry with materialdried with MgSO4
8. concentrationconcentrated
9. customto give the crude product, which
10. customwas purified by column chromatography (0-20% MeOH/DCM, monitor at 210 nm)

ORD-Eintrag

ord-415698b9b9e243e9b7477d1ce7c427dd

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08952166B2