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

HRID 2213037노트

반응식

HRID 2213037 반응식
[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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매2회HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-1ae89855c0de4cb392c501776948b8dd
출처 데이터셋
uspto-grants-2006_09
특허 번호
US07105507B2

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