Hydrochloric Acid → HCID 66751041, compound

HRID 408560Notes

Reaction equation

HRID 408560 reaction equation
Br[C:2]1[C:7]2[CH:8]=[CH:9][S:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:11]([CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])#[N:12].CC([O-])(C)C.[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:17]([O:16][C:14](=[O:15])[CH:13]([C:2]1[C:7]2[CH:8]=[CH:9][S:10][C:6]=2[CH:5]=[CH:4][CH:3]=1)[C:11]#[N:12])([CH3:20])([CH3:19])[CH3:18]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 70693tert-Butyl cyanoacetateHCID 120942084-Bromobenzo[b]thiopheneHCID 23665647Potassium tert-butoxide

Product 1

HCID 66751041HCID 66751041, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
20 °C

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.

Workup

  1. temperatureThe reaction was refluxed for 40 min
  2. temperatureThe resulting mixture was refluxed for 1.5 h under argon
  3. customthe reaction mixture was partitioned between water and EtOAc
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude was purified by chromatography on silica gel (elution with heptane/DCM: 9/1 to 1/1)

Sources & evidence

ORD record
ord-719985b2e402402b83bf0808ae4543fd
Source dataset
uspto-grants-2014_06
Patent number
US08759334B2

Reaction notes

Loading…