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

HRID 1848480Notes

Reaction equation

HRID 1848480 reaction equation
C(OC([NH:8][CH2:9][CH:10]([C:12]1([C:25]([O:27]C)=O)[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)[OH:11])=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(=O)([O-])[O-].[K+].[K+].C([O-])(O)=O.[Na+].O(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O>C(Cl)Cl>[OH:11][CH:10]1[C:12]2([CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)[C:25](=[O:27])[NH:8][CH2:9]1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 867094901-Tert-butyl 4-methyl 4-(2-((tert-butoxycarbonyl)amino)-1-hydroxyethyl)piperidine-1,4-dicarboxylate

Product 1

HCID 86709491tert-Butyl 4-hydroxy-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

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

Workup

  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)

Sources & evidence

ORD record
ord-415698b9b9e243e9b7477d1ce7c427dd
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

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