Sulfuric Acid → Tert-butyl 9-benzyl-2,2-dimethyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxylate

HRID 1689510Notes

Reaction equation

HRID 1689510 reaction equation
S(=O)(=O)(O)O.[CH2:6]([N:13]1[CH2:18][CH2:17][C:16]([CH2:20][NH:21][CH2:22][C:23]([CH3:25])=[CH2:24])([OH:19])[CH2:15][CH2:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:26](=[O:29])(O)[O-:27].[Na+]>C(#N)C>[CH2:6]([N:13]1[CH2:18][CH2:17][C:16]2([O:19][C:23]([CH3:25])([CH3:24])[CH2:22][N:21]([C:26]([O:27][C:7]([CH3:12])([CH3:8])[CH3:6])=[O:29])[CH2:20]2)[CH2:15][CH2:14]1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 579889841-Benzyl-4-((2-methylallylamino)methyl)piperidin-4-ol

Product 1

HCID 57989295Tert-butyl 9-benzyl-2,2-dimethyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Concentrated sulfuric acid (12 ml) was added to 1-benzyl-4-((2-methylallylamino)methyl)piperidin-4-ol (Example 271, step a) (2.2 g) and the mixture was allowed to stand for 2 hours at room temperature. The reaction mixture was treated with ice/water (100 mL) followed by solid sodium bicarbonate, portionwise, until the mixture was basic. Acetonitrile (50 mL) was added followed by BOC-anhydride (1.925 g) and the reaction mixture stirred at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate (×2) and the combined organics were dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography, eluting with 1% methanol in dichloromethane switching to 1% methanol in dichloromethane with 1% triethylamine. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.8 g.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate (×2)
  2. dry with materialthe combined organics were dried over sodium sulphate
  3. filtrationfiltered
  4. customthe solvent evaporated under reduced pressure
  5. customThe crude product was purified by flash silica chromatography
  6. washeluting with 1% methanol in dichloromethane switching to 1% methanol in dichloromethane with 1% triethylamine
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-8e6e40075a89491a87a86152f33a86af
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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