Potassium Hydroxide → Benzo[b]thiophene-5-acetic acid

HRID 2390966Notes

Reaction equation

HRID 2390966 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[S:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.CC(C)([O-])C.[K+].C([CH2:19][C:20]([O:22]C(C)(C)C)=[O:21])#N.[OH-].[K+]>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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.C(O)CO.COCCOC>[S:9]1[C:5]2[CH:4]=[CH:3][C:2]([CH2:19][C:20]([OH:22])=[O:21])=[CH:10][C:6]=2[CH:7]=[CH:8]1

Participants

10

Reactant 4

HCID 14797Potassium HydroxideHCID 70693tert-Butyl cyanoacetateHCID 27765785-Bromo-1-benzothiopheneHCID 23665647Potassium tert-butoxide

Product 1

HCID 11469582Benzo[b]thiophene-5-acetic acidYield 78%

Reagents, catalysts & solvents 5

HCID 11776TriphenylphosphineCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 174Ethylene GlycolSolventHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

To 1,2-dimethoxyethane (1.00 L) solution of 250 g of 5-bromobenzothiophene were added 276 g of potassium tert-butoxide and 174 g of tert-butyl cyanoacetate. Thereto were added 8.23 g of dichlorobis(triphenylphosphine)palladium(II) and 6.15 g of triphenylphosphine at 80 to 85° C., which was then refluxed for 2 hours. Next, to the reaction mixture were added 500 mL of ethylene glycol, 250 mL of water and 263 g of potassium hydroxide, which was then refluxed for 4 hours. To the reaction mixture were added 1.50 L of water and 12.5 g of kieselguhr (celipure, product of Advanced Minerals Company). After insoluble matter was filtered off, to the filtrate was added 250 mL of toluene, and the aqueous layer was separated. To the aqueous layer were added 375 mL of toluene and 375 mL of ethyl acetate, the pH was adjusted to 1 with 505 mL of hydrochloric acid, and the organic layer was separated. The organic layer was treated with 12.5 g of activated carbon. The solvent was distilled off under reduced pressure, to which was added toluene. The precipitate was collected by filtration to provide 176 g of 2-(1-benzothiophen-5-yl)acetic acid as white solid form.

Workup

  1. temperaturewhich was then refluxed for 2 hours
  2. temperaturewas then refluxed for 4 hours
  3. filtrationAfter insoluble matter was filtered off, to the filtrate
  4. additionwas added 250 mL of toluene
  5. customthe aqueous layer was separated
  6. additionTo the aqueous layer were added 375 mL of toluene and 375 mL of ethyl acetate
  7. customthe organic layer was separated
  8. additionThe organic layer was treated with 12.5 g of activated carbon
  9. distillationThe solvent was distilled off under reduced pressure, to which
  10. additionwas added toluene
  11. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-e489794dbc4b41c3a0fafa0f2a2dc14e
Source dataset
uspto-grants-2012_09
Patent number
US08273902B2

Reaction notes

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