Sodium Thiosulfate → Tert-butyl 1-oxa-5-azaspiro[2.3]hexane-5-carboxylate

HRID 876493Notes

Reaction equation

HRID 876493 reaction equation
[CH2:1]=[C:2]1[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.C1C=C(Cl)C=C(C(OO)=[O:21])C=1.[O-]S([O-])(=S)=O.[Na+].[Na+].C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.C(O)(C)C>[O:21]1[C:2]2([CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]2)[CH2:1]1

Participants

7

Reactant 4

HCID 24477Sodium ThiosulfateHCID 70297m-Chloroperbenzoic acid3×HCID 516892Sodium BicarbonateHCID 55269097tert-Butyl 3-methylideneazetidine-1-carboxylate

Product 1

HCID 66521770Tert-butyl 1-oxa-5-azaspiro[2.3]hexane-5-carboxylateYield 26.1%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolvent2×HCID 6212ChloroformSolvent

Procedure

To a 0° C. solution of tert-butyl 3-methyleneazetidine-1-carboxylate (3.50 g, 20.7 mmol) in 115 mL CHCl3 was added 77% mCPBA (13.9 g, 62.0 mmol) in 3 batches. Isopropyl alcohol (2 mL) was added. The reaction mixture was stirred for 10 minutes, then warmed to ambient temperature and stirred. After 19 hours, the milky reaction mixture was cooled to 0° C., 10 mL isopropyl alcohol was added (reaction mixture clarified), and another 1 equivalent of mCPBA was added. The reaction mixture was warmed to ambient temperature and stirred 2 hours, then another 1 equivalent mCPBA was added portionwise. After a total of 40 hours, the reaction mixture was cooled to 0° C., and 200 mL of 1:1 saturated Na2S2O3/saturated NaHCO3 was added slowly by pouring portionwise through ice (internal temperature was monitored; an initial 10° C. exotherm was observed). The mixture was stirred for 30 minutes, then extracted with CHCl3, and combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel (5-50% ethyl acetate in hexanes gradient) to give the desired product (1.0 g, 26.1% yield) as a clear colorless oil.

Workup

  1. stirringstirred
  2. waitAfter 19 hours
  3. customthe milky reaction mixture
  4. temperaturewas cooled to 0° C.
  5. custom(reaction mixture clarified)
  6. temperatureThe reaction mixture was warmed to ambient temperature
  7. stirringstirred 2 hours
  8. temperatureAfter a total of 40 hours, the reaction mixture was cooled to 0° C.
  9. additionby pouring portionwise through ice (internal temperature
  10. custom10° C. exotherm
  11. stirringThe mixture was stirred for 30 minutes
  12. extractionextracted with CHCl3
  13. dry with materialwere dried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe crude was purified on silica gel (5-50% ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-56b3294afa294014bd733ffa71119923
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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