Diethyl (cyanomethyl)phosphonate → tert-Butyl 4-(cyanomethylidene)piperidine-1-carboxylate

HRID 1876844Notes

Reaction equation

HRID 1876844 reaction equation
CC(C)([O-])C.[K+].[C:7]([CH2:9]P(=O)(OCC)OCC)#[N:8].O=[C:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1>O1CCCC1>[C:7]([CH:9]=[C:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)#[N:8]

Participants

5

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 15326949tert-Butyl 4-(cyanomethylidene)piperidine-1-carboxylateYield 97.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 1.0 M of potassium tert-butoxide in tetrahydrofuran (26.3 mL) at 0° C. was added dropwise a solution of diethyl cyanomethylphosphonate (4.47 mL, 0.0276 mol) in tetrahydrofuran (33.61 mL). The reaction was warmed to room temperature and then cooled to 0° C. again. To the reaction mixture was added a solution of tert-butyl 4-oxo-1-piperidinecarboxylate (5.0 g, 0.025 mol) in tetrahydrofuran (6.72 mL). The reaction was allowed to warm up to room temperature and stirred at room temperature overnight. After being quenched with water, the mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried and evaporated to dryness. The crude mixture was purified on silica gel, eluting with 0 to 60% EtOAc in hexanes, to give the desired product (5.40 g, 97%). LCMS (M+Na) 244.9.

Workup

  1. temperaturecooled to 0° C. again
  2. temperatureto warm up to room temperature
  3. customAfter being quenched with water
  4. extractionthe mixture was extracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. customdried
  7. customevaporated to dryness
  8. customThe crude mixture was purified on silica gel
  9. washeluting with 0 to 60% EtOAc in hexanes

Sources & evidence

ORD record
ord-d491dc48782346c5b3f104b214390db5
Source dataset
uspto-grants-2012_11
Patent number
US08309718B2

Reaction notes

Loading…