Sodium hydride → tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate

HRID 1525846Notes

Reaction equation

HRID 1525846 reaction equation
[I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[O:9]=[C:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1>CS(C)=O>[O:9]1[C:10]2([CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15]2)[CH2:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 22135564tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylateYield 59.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of trimethylsulfoxonium iodide (50.2 mmol) and anhydrous dimethyl sulfoxide (DMSO) (50 mL) was stirred at room temperature for 1 h. The reaction was then cooled to 0° C. and 60% sodium hydride in mineral oil (60.2 mmol) was added in small portions over several minutes. The reaction was allowed to warm to room temperature and stirred for 2 h. The resulting white slurry was cooled to 0° C. then treated with solid 1,1-dimethylethyl 4-oxo-1-piperidinecarboxylate (50.2 mmol) in one portion. The ice bath was removed and stirring continued at room temperature for 18 h. Ice cold water (150 mL) was added and the mixture was extracted into diethyl ether (3×). The extracts were washed with brine, dried (sodium sulfate) then evaporated under reduced pressure to a yellow oil. The oil was dissolved in ethyl acetate, treated with silica powder (˜20 g), and evaporated to dryness. This was placed on a short pad of silica in a sintered glass funnel and washed with hexanes (500 mL; the filtrate was discarded). The silica pad was then washed with 2:1 hexanes/ethyl acetate. The filtrate was evaporated in vacuo to give the title product (6.40 g, 57% yield) as a pale yellow oil that solidified upon standing. MS(ES)+ m/e 214.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 1.47 (s, 11 H) 1.72-1.87 (m, 2 H) 2.69 (s, 2H) 3.36-3.50 (m, 2 H) 3.63-3.83 (m, 2 H).

Workup

  1. temperatureThe reaction was then cooled to 0° C.
  2. temperatureto warm to room temperature
  3. stirringstirred for 2 h
  4. temperatureThe resulting white slurry was cooled to 0° C.
  5. customThe ice bath was removed
  6. stirringstirring
  7. waitcontinued at room temperature for 18 h
  8. additionIce cold water (150 mL) was added
  9. extractionthe mixture was extracted into diethyl ether (3×)
  10. washThe extracts were washed with brine
  11. dry with materialdried (sodium sulfate)
  12. customthen evaporated under reduced pressure to a yellow oil
  13. dissolutionThe oil was dissolved in ethyl acetate
  14. additiontreated with silica powder (˜20 g)
  15. customevaporated to dryness
  16. customThis was placed on a short pad of silica in a sintered glass funnel
  17. washwashed with hexanes (500 mL
  18. washThe silica pad was then washed with 2:1 hexanes/ethyl acetate
  19. customThe filtrate was evaporated in vacuo

Sources & evidence

ORD record
ord-d338af1afc1d4cfb88228173b0638f72
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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