Formamide → Tert-butyl 6,8-dioxo-2,5,7-triazaspiro[3.4]octane-2-carboxylate

HRID 1506351Notes

Reaction equation

HRID 1506351 reaction equation
O=[C:2]1[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[C:13](=[O:16])([O-])[O-].[NH4+:17].[NH4+].[C-]#N.[K+].[CH:22]([NH2:24])=[O:23].[Cl-].[Na+].[Cl-].[NH4+]>C(OCC)(=O)C>[O:23]=[C:22]1[NH:17][C:13](=[O:16])[C:2]2([CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]2)[NH:24]1

Participants

8

Reactant 6

HCID 713FormamideHCID 5234Sodium ChlorideHCID 9032Potassium CyanideHCID 25517Ammonium ChlorideHCID 517111Ammonium CarbonateHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 67168773Tert-butyl 6,8-dioxo-2,5,7-triazaspiro[3.4]octane-2-carboxylateYield 44%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A long sealed tube was charged with solid tert-butyl 3-oxoazetidine-1-carboxylate (2.500 g, 14.60 mmol), ammonium carbonate (9.82 g, 102 mmol), potassium cyanide (1.902 g, 29.2 mmol), and formamide (20 mL). The vessel was sealed and shaken back and forth until all of the solids were wetted and then placed in a 80° C. oil bath overnight behind a blast shield. The reaction vessel was cooled in an ice bath for 15 min and the contents of the vessel were carefully transferred to a separating funnel using ethyl acetate and saturated aq. sodium chloride to which ˜3 g of ammonium chloride had been added. The aqueous layer (200 mL) was extracted with ethyl acetate, dried over magnesium sulfate, filtered, concentrated to ˜10 mL of a yellow homogeneous liquid. The crude material was chromatographed on a 80 g SiO2 cartridge using pure ethyl acetate. The desired fractions were collected and concentrated in vacuo to give tert-butyl 6,8-dioxo-2,5,7-triazaspiro[3.4]octane-2-carboxylate (1.54 g, 44%) as a white solid. MS (M−1)=240. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.8 (1H, s), 8.48 (1H, s), 4.05 (2H, d), 3.39 (2H, d), 1.06 (9H, s).

Workup

  1. customThe vessel was sealed
  2. customplaced in a 80° C.
  3. customovernight
  4. temperatureThe reaction vessel was cooled in an ice bath for 15 min
  5. customthe contents of the vessel were carefully transferred to a separating funnel
  6. additionhad been added
  7. extractionThe aqueous layer (200 mL) was extracted with ethyl acetate
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to ˜10 mL of a yellow homogeneous liquid
  11. customThe crude material was chromatographed on a 80 g SiO2 cartridge
  12. customThe desired fractions were collected
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-853df5dd915a4fd4b93127e2bc9d56f0
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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