Hydrochloric Acid → Ethyl 3-(4-bromophenyl)-2-cyano-3-o-tolylpropanoate

HRID 1617503Notes

Reaction equation

HRID 1617503 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[C:5]([C:14]#[N:15])=[CH:6][C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=1)[CH3:2].[C:17]1([CH3:25])[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Mg]Cl.Cl>C1(C)C=CC=CC=1.C1COCC1>[CH2:1]([O:3][C:4](=[O:16])[CH:5]([C:14]#[N:15])[CH:6]([C:7]1[CH:8]=[CH:9][C:10]([Br:13])=[CH:11][CH:12]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[CH3:25])[CH3:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 367501Ethyl 3-(4-bromophenyl)-2-cyanoprop-2-enoateHCID 178424304HCID 178424304, compound

Product 1

HCID 67015643Ethyl 3-(4-bromophenyl)-2-cyano-3-o-tolylpropanoateYield 73%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 3-(4-bromo-phenyl)-2-cyano-acrylic acid ethyl ester (6.65 g) in toluene (50 mL) was added to a solution of o-tolylmagnesium chloride in THF (1M, 30.9) at 0° C. After the addition was complete, the solution was heated to 85° C. for 1.5 hours, and stirring was continued at rt overnight. The mixture was heated for additional 2 hours to 85° C., cooled and poured onto ice. 1M HCl was added, the phases were separated and the inorganic one was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (Et2O/n-heptane 1:3) to yield the title compound (6.45 g, 73%) as a light yellow oil, MS (ESI−): m/z=370.0444 ([M−H]−, 1Br).

Workup

  1. additionAfter the addition
  2. temperatureThe mixture was heated for additional 2 hours to 85° C.
  3. temperaturecooled
  4. additionpoured onto ice
  5. customthe phases were separated
  6. extractionthe inorganic one was extracted with EtOAc (2×)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by flash chromatography on silica gel (Et2O/n-heptane 1:3)

Sources & evidence

ORD record
ord-0351cf0fc309490b92fc09579787351f
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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