Potassium Carbonate → tert-Butyl 4-(cyanomethylidene)piperidine-1-carboxylate

HRID 604310Notes

Reaction equation

HRID 604310 reaction equation
[C:1]([CH2:3]P(=O)(OCC)OCC)#[N:2].C(=O)([O-])[O-].[K+].[K+].[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]>C1COCC1>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][C:28](=[CH:3][C:1]#[N:2])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 75676Diethyl (cyanomethyl)phosphonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 15326949tert-Butyl 4-(cyanomethylidene)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add diethyl cyanomethylphosphonate (5.33 g, 4.88 mL, 30.11 mmol) to potassium carbonate (3.47 g, 25.09 mmol) in dry THF (10 mL) and stir at room temperature for 15 min., then heat under reflux for 15 min. To this mixture add 4-oxopiperidine-1-carboxylic acid t-butyl ester (5.00, 25.09 mmol) and heat under reflux under nitrogen for 24 hr., allow to cool to room temperature and stand overnight. Pour the reaction mixture into aqueous potassium carbonate solution (10%, 80 mL) and extract the resultant mixture with ethyl acetate (2×50 mL). Combine the organics, dry (MgSO4) and evaporate in vacuo to give 4-cyanomethylenepiperidine-1-carboxylic acid t-butyl ester as a liquid which solidifies on standing (5.39 g, 96.6%). NMR (δ-CDCl3) 1.5 (s, 9H), 2.4 (m, 2H), 2.6 (m, 2H), 3.5 (m, 4H), 5.2 (s, 1H).

Workup

  1. temperatureheat
  2. temperatureunder reflux for 15 min
  3. temperatureheat
  4. temperatureunder reflux under nitrogen for 24 hr
  5. temperatureto cool to room temperature
  6. waitstand overnight
  7. extractionextract the resultant mixture with ethyl acetate (2×50 mL)
  8. dry with materialCombine the organics, dry (MgSO4)
  9. customevaporate in vacuo

Sources & evidence

ORD record
ord-2b78248759324a07b2e7ae9d5b8b8c19
Source dataset
uspto-grants-2011_03
Patent number
US07910588B2

Reaction notes

Loading…