Potassium Cyanide → HCID 67354921, compound

HRID 2059916Notes

Reaction equation

HRID 2059916 reaction equation
[NH:1]1[CH2:4][CH2:3][CH2:2]1.O=[C:6]1[CH2:23][CH2:22][C:9]2([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH2:8][CH2:7]1.[C-]#N.[K+].[C:27]1([Mg]Br)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CO.C(O)(=O)C.C1COCC1>[N:1]1([C:6]2([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:23][CH2:22][C:9]3([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]3)[CH2:8][CH2:7]2)[CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 9032Potassium CyanideHCID 10422AzetidineHCID 51072194tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylateHCID 178418255HCID 178418255, compound

Product 1

HCID 67354921HCID 67354921, compoundYield 22%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Azetidine (29.9 mmol, 10 eq) was added to a solution of tert-butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (2.99 mmol, 1 eq) in methanol (15 ml) and acetic acid (1.5 ml) at 0° C. Then potassium cyanide (7.47 mmol, 2.5 eq) was added to the reaction mixture and it was stirred for another 16 h. The reaction mixture was slowly quenched with NH4OH solution (50 g ice+50 ml ammonia liquor) and stirred at 0° C. for another 30 min. The mixture was extracted with ethyl acetate. The organic layer was washed with water (15 ml), saturated ferrous sulfate solution (15 ml) and brine (20 ml) successively, dried over Na2SO4 and concentrated under reduced pressure to give the crude product. A solution of the crude product (1.1 g) in THF (30 ml) was added to an ice-cold solution of phenyl magnesium bromide (5 eq., 1 M solution in THF) and the resulting reaction mixture was stirred at 25° C. for 16 h under a nitrogen atmosphere. The reaction mixture was quenched with saturated ammonia solution under ice-cold conditions and extracted with ethyl acetate. The organic layer was washed with water (10 ml) and brine (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography (25% EtOH in hexanes) to yield the desired product. Yield: 22%

Workup

  1. customThe reaction mixture was slowly quenched with NH4OH solution (50 g ice+50 ml ammonia liquor)
  2. stirringstirred at 0° C. for another 30 min
  3. extractionThe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with water (15 ml), saturated ferrous sulfate solution (15 ml) and brine (20 ml) successively
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude product
  8. customthe resulting reaction mixture
  9. stirringwas stirred at 25° C. for 16 h under a nitrogen atmosphere
  10. customThe reaction mixture was quenched with saturated ammonia solution under ice-cold conditions
  11. extractionextracted with ethyl acetate
  12. washThe organic layer was washed with water (10 ml) and brine (10 ml)
  13. dry with materialdried over anhydrous sodium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customto give the crude product
  16. customThe crude product was purified by silica gel column chromatography (25% EtOH in hexanes)

Sources & evidence

ORD record
ord-8c4ecf1ae97b4bdfb92a86b15473d459
Source dataset
uspto-grants-2012_10
Patent number
US08278319B2

Reaction notes

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