Acetone → Tert-butyl 1-oxo-2-oxa-8-azaspiro[4.5]decane-8-carboxylate

HRID 2213022Notes

Reaction equation

HRID 2213022 reaction equation
C([C:4]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)C=C.ClCCl.[BH4-].[Na+].CC(C)=O>CO.O>[O:18]=[C:17]1[C:4]2([CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])[CH2:8][CH2:9]2)[CH2:21][CH2:20][O:19]1

Participants

7

Reactant 4

HCID 180AcetoneHCID 6344DichloromethaneHCID 4311764Sodium borohydride2×HCID 162182701-tert-Butyl 4-ethyl 4-(prop-2-en-1-yl)piperidine-1,4-dicarboxylate

Product 1

HCID 10015228Tert-butyl 1-oxo-2-oxa-8-azaspiro[4.5]decane-8-carboxylateYield 88%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
-78 °C

Procedure

1-(1,1-Dimethylethyl) 4-ethyl 4-(2-propenyl)-1,4-piperidinedicarboxylate (Description 82, 20.0 g, 67.2 mmol) was dissolved in methanol (300 mL) and dichloromethane (300 mL) and cooled to −78° C. Oxygen was bubbled through the solution for 10 minutes, then ozone for 75 minutes, to give a persistant blue coloration. Oxygen was bubbled through the solution for 10 minutes, then nitrogen for 10 minutes. Sodium borohydride (5.1 g, 135 mmol) was added and the mixture was stirred at −78° C. for 1 hour. Further sodium borohydride (5.1 g, 135 mmol) was added and the mixture was stirred at room temperature for 16 hours. Acetone (75 mL) was added and the mixture was stirred at room temperature for 10 minutes. Water (50 mL) was added and the organic solvent was evaporated under reduced pressure. Saturated aqueous ammonium chloride (500 mL) was added and the mixture was extracted with ethyl acetate (2×500 mL). The combined organic fractions were washed with aqueous citric acid (10%, 500 mL), saturated aqueous sodium hydrogen carbonate (500 mL) and brine (200 mL), dried (Na2SO4) and the solvent was evaporated under reduced pressure to give the title compound (15.0 g, 88%). 1H NMR (400 MHz, CDCl3) δ 4.31 (2H, t, J 7 Hz), 3.97–3.87 (2H, m), 3.17–3.07 (2H, m), 2.20 (2H, t, J 7 Hz), 1.92–1.82 (2H, m), 1.60–1.45 (2H, m), and 1.45 (9H, s).

Workup

  1. customOxygen was bubbled through the solution for 10 minutes
  2. customto give a persistant blue coloration
  3. customOxygen was bubbled through the solution for 10 minutes
  4. waitnitrogen for 10 minutes
  5. stirringthe mixture was stirred at room temperature for 16 hours
  6. stirringthe mixture was stirred at room temperature for 10 minutes
  7. customthe organic solvent was evaporated under reduced pressure
  8. additionSaturated aqueous ammonium chloride (500 mL) was added
  9. extractionthe mixture was extracted with ethyl acetate (2×500 mL)
  10. washThe combined organic fractions were washed with aqueous citric acid (10%, 500 mL), saturated aqueous sodium hydrogen carbonate (500 mL) and brine (200 mL)
  11. dry with materialdried (Na2SO4)
  12. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-93c14db2b7bf4429b3d205c0f23f4caf
Source dataset
uspto-grants-2006_09
Patent number
US07105507B2

Reaction notes

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