Ethyl cyanoacetate → Ethyl 3-(4-bromophenyl)-2-cyanoacrylate

HRID 1527960Notes

Reaction equation

HRID 1527960 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[C:10]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])#[N:11]>C1(C)C=CC=CC=1.N1CCCCC1>[Br:1][C:2]1[CH:9]=[CH:8][C:5](/[CH:6]=[C:12](\[C:10]#[N:11])/[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 7764Ethyl cyanoacetateHCID 707414-Bromobenzaldehyde

Product 1

HCID 5378084Ethyl 3-(4-bromophenyl)-2-cyanoacrylateYield 27.4%

Reagents, catalysts & solvents 2

HCID 8082PiperidineCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 4-bromobenzaldehyde (106 g, 573 mmol) in toluene (1000 mL) were added ethyl 2-cyanoacetate (71.3 g, 630 mmol) and piperidine (976 mg, 11.5 mmol) and the clear, light brown solution was heated at reflux for 5 h in a 4-neck flask equipped with a Dean-Stark trap, then stirred overnight at room temperature. After cooling the reaction mixture was evaporated, the residue suspended in heptane (500 mL), homogenized in an ultrasound bath for min, stirred for 20 min at 50° C., then the precipitate was collected by filtration. This was dissolved in ethyl acetate (1000 mL) and heptane (500 mL), then slowly concentrated at 50° C. to a volume of approximately 300 mL of solvent. This solution started to crystallize upon standing. The precipitate (96 g) was collected by filtration and washed with heptane/ethyl acetate 9:1 (300 mL). The mother liquor was concentrated at 50° C. until crystallization started. The product was allowed to precipitate over 1 h at room temperature, then collected by filtration to produce a second crop of product (44 g). Total yield: 140 g (87%). Light yellow solid, MS: 299.1 [M+H]+.

Workup

  1. temperaturethe clear, light brown solution was heated
  2. temperatureat reflux for 5 h in a 4-neck flask
  3. customequipped with a Dean-Stark trap
  4. temperatureAfter cooling the reaction mixture
  5. customwas evaporated
  6. stirringhomogenized in an ultrasound bath for min
  7. stirringstirred for 20 min at 50° C.
  8. filtrationthe precipitate was collected by filtration
  9. dissolutionThis was dissolved in ethyl acetate (1000 mL)
  10. concentrationheptane (500 mL), then slowly concentrated at 50° C. to a volume of approximately 300 mL of solvent
  11. customto crystallize
  12. filtrationThe precipitate (96 g) was collected by filtration
  13. washwashed with heptane/ethyl acetate 9:1 (300 mL)
  14. concentrationThe mother liquor was concentrated at 50° C. until crystallization
  15. customto precipitate over 1 h at room temperature
  16. filtrationcollected by filtration

Sources & evidence

ORD record
ord-bbcfd2f0b830499993849b1349337e05
Source dataset
uspto-grants-2015_07
Patent number
US09090565B2

Reaction notes

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