Water → tert-Butyl 8-oxo-5-azaspiro(2.5)octane-5-carboxylate

HRID 1016156Notes

Reaction equation

HRID 1016156 reaction equation
[CH3:1][C:2](C)([O-])C.[K+].[O:7]=[C:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.[I-].ClCC[S+](C)C.O>C(O)(C)(C)C>[O:7]=[C:8]1[C:9]2([CH2:2][CH2:1]2)[CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH2:13]1

Participants

6

Reactant 4

HCID 962WaterHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 10912030(2-Chloroethyl)diMethylsulfoniuM iodideHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 57889898tert-Butyl 8-oxo-5-azaspiro(2.5)octane-5-carboxylateYield 20.34%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent2×

Procedure

A solution of potassium tert-butoxide (3.26 g, 27.6 mmol) in tert-butanol (40 mL) was treated with tert-butyl 4-oxopiperidine-1-carboxylate (5 g, 25.09 mmol), causing the reaction to turn bright orange. The mixture was stirred for 1 h, then treated with (2-chloroethyl)dimethylsulfonium iodide (5.70 g, 22.59 mmol), added in three portions at 10 minute intervals. This addition caused the color of the reaction to gradually fade to pale yellow. The mixture was stirred for 2 hours, then diluted with tert-butanol (10 mL), treated with potassium tert-butoxide (2.96 g, 25.09 mmol), and stirred overnight at room temperature. The reaction was poured into water (100 mL) and extracted 3× with 100 mL ethyl acetate. The combined organic phases were washed with water and brine, then dried over sodium sulfate and concentrated in-vacuo. The residue was purified over a 5×15 cm silica gel column, eluting with ethyl acetate/hexanes (10%-15%-20%-25% EtOAc, 1 L at each concentration), to yield the title compound (1.15 g, 5.10 mmol, 20.34% yield) as a colorless oil.

Workup

  1. customthe reaction
  2. additionadded in three portions at 10 minute intervals
  3. additionThis addition
  4. customthe color of the reaction
  5. stirringThe mixture was stirred for 2 hours
  6. stirringstirred overnight at room temperature
  7. extractionextracted 3× with 100 mL ethyl acetate
  8. washThe combined organic phases were washed with water and brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated in-vacuo
  11. customThe residue was purified over a 5×15 cm silica gel column
  12. washeluting with ethyl acetate/hexanes (10%-15%-20%-25% EtOAc, 1 L
  13. concentrationat each concentration),

Sources & evidence

ORD record
ord-73bec7b6c3bf4ae1b44f8e306841eb2f
Source dataset
uspto-grants-2011_07
Patent number
US07985861B2

Reaction notes

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