Ethyl Acetate → 1-(tert-Butoxycarbonyl)-3-(cyanomethylene)azetidine

HRID 1966131Notes

Reaction equation

HRID 1966131 reaction equation
[H-].[Na+].[C:3]([CH2:5]P(=O)(OCC)OCC)#[N:4].O=[C:15]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1.C(OCC)(=O)C>O1CCCC1.[Cl-].[Na+].O>[C:3]([CH:5]=[C:15]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1)#[N:4]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 457892161-(tert-Butoxycarbonyl)-3-(cyanomethylene)azetidine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a suspension of sodium hydride (60% dispersion in mineral oil, 0.257 g, 6.42 mmol) in tetrahydrofuran (32 mL) at 0° C. under a nitrogen atmosphere was added diethyl cyanomethylphosphonate (1.19 g, 6.72 mmol) (purchased from Aldrich). The reaction was then stirred for 45 minutes at room temperature. A solution of tert-butyl 3-oxoazetidine-1-carboxylate (1.00 g, 5.84 mmol) (purchased from Alfa Aesar) in tetrahydrofuran (8.8 mL) was introduced dropwise and the mixture was stirred for 16 hours. Brine and ethyl acetate were added and the layers separated. The aqueous layer was extracted with three portions of ethyl acetate. The combined extracts were dried over sodium sulfate, filtered and concentrated to afford product, used without further purification in Step 2 (1.12 g, 99%).

Workup

  1. stirringthe mixture was stirred for 16 hours
  2. customthe layers separated
  3. extractionThe aqueous layer was extracted with three portions of ethyl acetate
  4. dry with materialThe combined extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford product
  8. customused without further purification in Step 2 (1.12 g, 99%)

Sources & evidence

ORD record
ord-255cbde689004bb9bf793a8dc5c417cc
Source dataset
uspto-grants-2013_04
Patent number
US08420629B2

Reaction notes

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