Diethyl (cyanomethyl)phosphonate → 1-(tert-Butoxycarbonyl)-3-(cyanomethylene)azetidine

HRID 1049123Notes

Reaction equation

HRID 1049123 reaction equation
CC(C)([O-])C.[K+].[C:7]([CH2:9]P(=O)(OCC)OCC)#[N:8].O=[C:19]1[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:20]1>O1CCCC1>[C:7]([CH:9]=[C:19]1[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:20]1)#[N:8]

Participants

5

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 23665647Potassium tert-butoxide

Product 1

HCID 457892161-(tert-Butoxycarbonyl)-3-(cyanomethylene)azetidineYield 95.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 1.0 M potassium tert-butoxide in tetrahydrofuran (30.7 mL, 30.7 mmol) at 0° C. was added dropwise a solution of diethyl cyanomethylphosphonate (5.20 mL, 32.2 mmol) in tetrahydrofuran (39 mL). The reaction was warmed to room temperature and then cooled at 0° C. again. To the reaction mixture was added a solution of tert-butyl 3-oxoazetidine-1-carboxylate (5.0 g, 0.029 mol, from Aldrich) in tetrahydrofuran (8 mL). The reaction was allowed to warm to room temperature and stirred overnight. After quenched with water, the mixture was extracted with ethyl acetate (EtOAc). The combined organic layers were washed with brine, dried over MgSO4, and evaporated under reduced pressure. The crude mixture was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexanes (0-70%) to give the desired product (5.40 g, 95%). LCMS cacld. for C10H14N2O2Na (M+Na)+: m/z=217.1. Found: 217.1

Workup

  1. temperaturecooled at 0° C. again
  2. temperatureto warm to room temperature
  3. customAfter quenched with water
  4. extractionthe mixture was extracted with ethyl acetate (EtOAc)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. customevaporated under reduced pressure
  8. customThe crude mixture was purified by flash chromatography on a silica gel column
  9. washeluting with ethyl acetate in hexanes (0-70%)

Sources & evidence

ORD record
ord-a50f8c00add340a08a9cb319930967a8
Source dataset
uspto-grants-2016_07
Patent number
US09382231B2

Reaction notes

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