Reaction #495742

Reaction equation

triphenylphosphine

4-bromobenzothiophene

tert-butyl cyanoacetate

t-BuOK

HCl

→

benzo[b]thiophen-4-yl-cyano-acetic acid tert-butyl ester

Solvents

DME

Conditions

Workup

1. 1
   TemperatureThe reaction was refluxed for 40 min
2. 2
   TemperatureThe resulting mixture was refluxed for 1.5 h under argon
3. 3
   Otherthe reaction mixture was partitioned between water and EtOAc
4. 4
   OtherThe organic layer was separated
5. 5
   Dryingdried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   OtherThe crude was purified by chromatography on silica gel (elution with heptane/DCM: 9/1 to 1/1)

Procedure

To a solution of 4-bromobenzothiophene (1 eq.) in DME were added tert-butyl cyanoacetate (1.1 eq.) and t-BuOK (2 eq.). The reaction was refluxed for 40 min. Thereto were added dichlorobis(triphenylphosphine)palladium(II) (0.02 eq.) and triphenylphosphine (0.06 eq.). The resulting mixture was refluxed for 1.5 h under argon and then cooled to 20° C. Aqueous HCl (6N) was added dropwise until pH=1 and the reaction mixture was partitioned between water and EtOAc. The organic layer was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with heptane/DCM: 9/1 to 1/1) to afford benzo[b]thiophen-4-yl-cyano-acetic acid tert-butyl ester.

Source