Ethyl cyanoacetate → Ethyl 4-cyanooxane-4-carboxylate

HRID 1748302Notes

Reaction equation

HRID 1748302 reaction equation
[H-].[Na+].[C:3]([CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])#[N:4].Cl[CH2:12][CH2:13][O:14][CH2:15][CH2:16]Cl>CN(C=O)C>[C:3]([C:5]1([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)#[N:4]

Participants

5

Reactant 3

HCID 7764Ethyl cyanoacetateHCID 8115Bis(2-chloroethyl) etherHCID 24758Sodium hydride

Product 1

HCID 22061355Ethyl 4-cyanooxane-4-carboxylateYield 28%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of NaH (22.11 g, 552.1 mmol) in DMF (350 mL) is added ethyl cyanoacetate (23.5 mL, 195 mmol) at 0° C. over 25 min. The reaction mixture is warmed to room temperature for 2 h and it is cooled down to 0° C. again. A solution of 1-chloro-2-(2-chloroethoxy)ethane (31.1 mL, 265.4 mmol) in DMF (50 mL) is added and the reaction mixture is warmed to room temperature for 1 h. Then the reaction mixture is heated at 90° C. for 16 h before the reaction is quenched with ice cold water (180 mL). The mixture is extracted with EtOAc (2×200 mL) and the organic layers are combined, dried (Na2SO4) and concentrated. The crude compound is purified by fractional distillation under high vacuum to afford the title compound (10 g, 25%) as a colorless oil.

Workup

  1. temperatureit is cooled down to 0° C. again
  2. temperaturethe reaction mixture is warmed to room temperature for 1 h
  3. temperatureThen the reaction mixture is heated at 90° C. for 16 h before the reaction
  4. customis quenched with ice cold water (180 mL)
  5. extractionThe mixture is extracted with EtOAc (2×200 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. distillationThe crude compound is purified by fractional distillation under high vacuum

Sources & evidence

ORD record
ord-17b3c00175c9400b96a8335164aacb84
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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