Ethyl cyanoacetate → Ethyl 2-cyano-3-(2,3-dichlorophenyl)propanoate

HRID 510424Notes

Reaction equation

HRID 510424 reaction equation
[C:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].Br[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=1[Cl:18].C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[C:1]([CH:3]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=1[Cl:18])[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2]

Participants

5

Reactant 3

HCID 7764Ethyl cyanoacetateHCID 11430Potassium CarbonateHCID 27346021-(Bromomethyl)-2,3-dichlorobenzene

Product 1

HCID 71270754Ethyl 2-cyano-3-(2,3-dichlorophenyl)propanoateYield 18.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of ethyl 2-cyanoacetate (4.52 g, 40 mmol), 1-(bromomethyl)-2,3-dichlorobenzene (4.8 g, 20 mmol) and potassium carbonate (11.04 g, 80 mmol) in THF (80 mL) was under reflux for 30 h. After cooled to room temperature, the solvent was removed in vacuo and the resulting mixture was acidified with 2 N hydrochloric acid. The resulting solution was extracted with ethyl acetate (80 mL×3). The combined organic layers were washed with water and brine, dried over sodium sulphate, concentrated under reduced pressure. The residue was crystallized with MeOH to give the titled product (1.0 g, 18%) as a white solid. The mother liquor was concentrated in vacuo and the residue was purified by a silica gel chromatography eluted with PE/EA=20/1 to give the titled product (1.53 g, 33%) as a colorless oil; LC/MS: MS (ES+) m/e 272 (MH+); 1H NMR (300 MHz, CDCl3) δ ppm 1.31 (t, J=7.2 Hz, 3H), 3.24 (dd, J=9.6, 13.8 Hz, 1H), 3.56 (dd, J=6.3, 13.8 Hz, 1H), 3.90-3.96 (dd, J=6.3, 9.6 Hz, 1H), 4.28 (dq, J=0.9, 7.2 Hz, 2H), 7.18-7.29 (m, 2H), 7.44 (dd, J=1.8, 7.8 Hz, 1H).

Workup

  1. temperatureunder reflux for 30 h
  2. customthe solvent was removed in vacuo
  3. extractionThe resulting solution was extracted with ethyl acetate (80 mL×3)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was crystallized with MeOH

Sources & evidence

ORD record
ord-cb22ec4fdc984655a39557772296fa9e
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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