Sodium hydride → 1-(1,1-Dimethylethyl) 2-ethyl 4-(cyanomethylene)-1,2-piperidinedicarboxylate

HRID 1073090Notes

Reaction equation

HRID 1073090 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]#[N:13])(=O)OCC)C.O=[C:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH:17]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:16]1>C1COCC1>[C:12]([CH:11]=[C:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH:17]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:16]1)#[N:13]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 159282621-Tert-butyl 2-ethyl 4-oxopiperidine-1,2-dicarboxylate

Product 1

HCID 542786301-(1,1-Dimethylethyl) 2-ethyl 4-(cyanomethylene)-1,2-piperidinedicarboxylateYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 0.75 g (0.019 mol, 60% by weight in oil) of sodium hydride (washed three times with hexanes) in 40 ml of THF was added 3.34 g (0.019 mol) of diethylcyanomethylphosphonate. After stirring the reaction mixture for thirty minutes at room temperature, a solution of 4.26 g (0.016 mol) of ethyl 4-oxo-N-t-butoxycarbonyl-2-piperidinecarboxylate in 10 ml of THF was added. The mixture was stirred for 30 minutes at room temperature and 90 minutes at the reflux temperature of the reaction mixture, then cooled to room temperature and quenched with water. The organic layer was separated and the aqueous layer extracted twice with diethyl ether. The organic extracts were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum. High pressure liquid chromatography of the residue afforded 3.58 g of ethyl 4-cyanomethylidene-N-t-butoxycarbonyl-2-piperidinecarboxylate.

Workup

  1. stirringThe mixture was stirred for 30 minutes at room temperature and 90 minutes at the reflux temperature of the reaction mixture
  2. temperaturecooled to room temperature
  3. customquenched with water
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted twice with diethyl ether
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-c7fb9a0c506e4ed6bdb31d40b1207761
Source dataset
uspto-grants-1990_11
Patent number
US04968678

Reaction notes

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