Hydrogen Peroxide → Tert-butyl 3-hydroxy-1-oxa-9-azaspiro[5.5]undecane-9-carboxylate

HRID 2213037Notes

Reaction equation

HRID 2213037 reaction equation
[O:1]1CCCC1.B.[O:7]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)[CH2:11][CH:10]=[CH:9][CH2:8]1.[OH-].[Na+].OO>O1CCCC1.C(OCC)C.O>[OH:1][CH:9]1[CH2:10][CH2:11][C:12]2([CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]2)[O:7][CH2:8]1

Participants

8

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 21955282Tert-butyl 1-oxa-9-azaspiro[5.5]undec-3-ene-9-carboxylate

Product 1

HCID 21955274Tert-butyl 3-hydroxy-1-oxa-9-azaspiro[5.5]undecane-9-carboxylateYield 24.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Borane tetrahydrofuran complex (1M in tetrahydrofuran, 23.68 mL, 23.68 mmol) was added dropwise to a solution of 1,1-dimethylethyl 1-oxa-9-azaspiro[5.5]undec-3-en-9-carboxylate (Description 131, 2.0 g, 7.89 mmol) in tetrahydrofuran (30 mL) and the mixture was stirred at room temperature for 6.5 hours. Water (25 mL), aqueous sodium hydroxide (4M, 25 mL) and hydrogen peroxide (37%, 25 mL) were added and the mixture was stirred at room temperature for 20 minutes. Water (100 mL) and diethyl ether (100 mL) were added and the layers were separated. The aqueous fraction was extracted with diethyl ether (100 mL) and the combined organic fractions were washed with brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate. The residue was purified by MPLC on silica gel, eluting with ethyl acetate, to give 1,1-dimethylethyl 3-hydroxy-1-oxa-9-azaspiro[5.5]undecane-9-carboxylate (520 mg, 24%); 1H NMR (360 MHz, CDCl3) δ 3.76–3.71 (4H, m), 3.50–3.45 (1H, m), 3.16–3.07 (2H, m), 1.92–1.85 (3H, m), 1.75–1.63 (2H, m), 1.46 (9H, s), and 1.45–1.35 (3H, m); and 1,1-dimethylethyl 4-hydroxy-1-oxa-9-azaspiro[5.5]undecane-9-carboxylate (200 mg, 9%);. 1H NMR (400 MHz, CDCl3) δ 4.02–3.93 (1H, m), 3.87–3.83 (1H, m), 3.75–3.71 (2H, m), 3.57 (1H, dt, J 2.3, 11.7 Hz), 3.19 (1H, t, J 11.3 Hz), 3.03 (1H, t, J 11.7 Hz), 1.95–1.87 (2H, m), 1.86–1.81 (1H, m), 1.68–1.65 (1H, m), 1.57–1.47 (2H, m), 1.45 (9H, s), and 1.41–1.28 (2H, m).

Workup

  1. stirringthe mixture was stirred at room temperature for 20 minutes
  2. customthe layers were separated
  3. extractionThe aqueous fraction was extracted with diethyl ether (100 mL)
  4. washthe combined organic fractions were washed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with ethyl acetate
  9. customThe residue was purified by MPLC on silica gel
  10. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-1ae89855c0de4cb392c501776948b8dd
Source dataset
uspto-grants-2006_09
Patent number
US07105507B2

Reaction notes

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