Ethyl cyanoacetate → Benzo[b]thiophene-5-acetic acid

HRID 2390964Notes

Reaction equation

HRID 2390964 reaction equation
CC(C)([O-])C.[K+].[C:7]([CH2:9][C:10]([O:12]CC)=[O:11])#N.BrC1[CH:17]=[CH:18][C:19]2[S:23][CH:22]=[CH:21][C:20]=2[CH:24]=1.[OH-].[Na+]>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.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[BH4-].[Na+].O.C(O)C.C1(C)C=CC=CC=1>[S:23]1[C:19]2[CH:18]=[CH:17][C:7]([CH2:9][C:10]([OH:12])=[O:11])=[CH:24][C:20]=2[CH:21]=[CH:22]1

Participants

12

Reactant 4

HCID 7764Ethyl cyanoacetateHCID 14798Sodium Hydroxide2×HCID 27765785-Bromo-1-benzothiopheneHCID 23665647Potassium tert-butoxide

Product 1

HCID 11469582Benzo[b]thiophene-5-acetic acidYield 74.9%

Reagents, catalysts & solvents 7

HCID 11776TriphenylphosphineCatalystHCID 4311764Sodium borohydrideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent2×

Procedure

To toluene (25 mL) suspension of 0.16 g of dichlorobis(triphenylphosphine)palladium(II) were added 0.12 g of triphenylphosphine, 0.01 g of sodium borohydride, 5.79 g of potassium tert-butoxide and 2.92 g of ethyl cyanoacetate, which was then stirred at room temperature for 10 minutes. Thereto were added 5.00 g of 5-bromobenzothiophene and 25 mL of toluene, which was then refluxed for 4 hours. Thereto was added 0.14 g of tetrakis(triphenylphosphine)palladium(0), which was then refluxed for 2 hours. Next, to the reaction solution were added 25 mL of ethanol, 2.82 g of sodium hydroxide and 5 mL of water, which was then refluxed for 6 hours. Thereto was added 2.82 g of sodium hydroxide, which was then refluxed for 5 hours. To the reaction mixture were added 15 mL of water and 0.5 g of activated carbon, and insoluble matter was filtered off. The aqueous layer was separated, and to the solution was added 35 mL of ethanol. The pH was adjusted to 2 with 15 mL of hydrochloric acid. Thereto was added 15 mL of water, which was then stirred at 40° C. Thereto was added 30 mL of water, which was stirred. After that, it was cooled. The precipitate was collected by filtration to provide 3.38 g of 2-(1-benzothiophen-5-yl)acetic acid as pale yellow solid form.

Workup

  1. temperaturewas then refluxed for 4 hours
  2. temperaturewas then refluxed for 2 hours
  3. temperaturewas then refluxed for 6 hours
  4. temperaturewas then refluxed for 5 hours
  5. filtrationwas filtered off
  6. customThe aqueous layer was separated
  7. additionto the solution was added 35 mL of ethanol
  8. additionThereto was added 15 mL of water, which
  9. stirringwas then stirred at 40° C
  10. additionThereto was added 30 mL of water, which
  11. stirringwas stirred
  12. temperatureAfter that, it was cooled
  13. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-61efb90e244e46f69ca76915f0db613a
Source dataset
uspto-grants-2012_09
Patent number
US08273902B2

Reaction notes

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