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

HRID 2363276Notes

Reaction equation

HRID 2363276 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, 0.0307 mol) at 0° C. was added dropwise a solution of diethyl cyanomethylphosphonate (5.20 mL, 0.0322 mol) in tetrahydrofuran (39.12 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, Aldrich: Cat. #696315) in tetrahydrofuran (7.82 mL). The reaction was allowed to warm to room temperature and stirred overnight. After quenched with water, the mixture was extracted with ethyl acetate. 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 with ethyl acetate in hexanes (0-70%) to give the desired product (5.40 g, 95%). LCMS (M+Na)+: m/z=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
  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 with ethyl acetate in hexanes (0-70%)

Sources & evidence

ORD record
ord-33e07634626a4936a65b691e3672c58a
Source dataset
uspto-grants-2014_04
Patent number
US08691807B2

Reaction notes

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