Diethyl Carbonate → Ethyl (3-chlorophenyl)(cyano)acetate

HRID 1865301Notes

Reaction equation

HRID 1865301 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5][C:6]#[N:7].[H-].[Na+].[C:13](=O)([O:17]CC)[O:14][CH2:15][CH3:16]>C1COCC1>[CH2:15]([O:14][C:13](=[O:17])[CH:5]([C:4]1[CH:8]=[CH:9][CH:10]=[C:2]([Cl:1])[CH:3]=1)[C:6]#[N:7])[CH3:16]

Participants

5

Reactant 3

HCID 7766Diethyl CarbonateHCID 24758Sodium hydrideHCID 73722m-Chlorophenylacetonitrile

Product 1

HCID 14113561Ethyl (3-chlorophenyl)(cyano)acetateYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

step 1—A solution 3-chlorobenzyl cyanide (10 g, 66 mmol) dissolved in diethyl carbonate (80 mL) was added over 15 min to a suspension of NaH (8.7 g, 0.218 mol, 60% dispersion in oil) in THF (70 mL) cooled to 0° C. The resulting mixture was stirred at RT for 12 h, heated at reflux for 14 h then cooled to RT and quenched with H2O. The reaction mixture was partitioned between Et2O and H2O and the aqueous layer was adjusted to pH 3 with 2M aqueous HCl and thrice back-extracted with Et2O. The combined organic layers were washed with water, brine, dried (Na2SO4), filtered and evaporated to afford 10.1 g (68% yield) of (3-chloro-phenyl)-cyano-acetic acid ethyl ester which was used in the next step without purification.

Workup

  1. temperatureheated
  2. temperatureat reflux for 14 h
  3. temperaturethen cooled to RT
  4. customquenched with H2O
  5. customThe reaction mixture was partitioned between Et2O and H2O
  6. extractionback-extracted with Et2O
  7. washThe combined organic layers were washed with water, brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-707faa0e49ac4f4dad3fcf0f120f69a4
Source dataset
uspto-grants-2009_12
Patent number
US07625905B2

Reaction notes

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