Ethyl bromoacetate → 2-Methylthiophene-3-carboxylic acid

HRID 1814506Notes

Reaction equation

HRID 1814506 reaction equation
C(N1CCN(C2C3[CH:15]=[CH:16][S:17][C:13]=3[CH:12]=C(C3C=CC(O)=CC=3)N=2)CC1)C.[H-].[Na+].[H][H].Br[CH2:30][C:31]([O:33]CC)=[O:32]>CN(C=O)C>[CH3:12][C:13]1[S:17][CH:16]=[CH:15][C:30]=1[C:31]([OH:33])=[O:32]

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 1357190444-(4-Ethylpiperazin-1-yl)-6-(4-hydroxyphenyl)thieno[3,2-c]pyridineHCID 178418361HCID 178418361, compound

Product 1

HCID 46254092-Methylthiophene-3-carboxylic acidYield 154.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

4-(4-Ethylpiprazin-1-yl)-6-(4-hydroxyphenyl)thieno[3,2-c]pyridine (1.10 g) was dissolved in DMF (30 ml), followed by the addition of 60% sodium hydride (0.18 g). After the evolution of hydrogen was ceased, ethyl bromoacetate (0.55 g) was added thereto, which was then stirred at 0° C. for 30 min. The reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with water, dried and evaporated. The resulting residue was dissolved in THF (30 ml), followed by the addition of 3M methylmagnesium bromide/ether solution (3.3 ml) under ice-cooling, and the mixture was reacted at room temperature for 1.5 hr. The reaction solution was partitioned between ethyl acetate and water, and the aqueous layer was extracted from the organic layer with 2N hydrochloric acid. The aqueous layer was basified with 2N sodium hydroxide and back-extracted with ethyl acetate. The organic layer was washed with water, dried and evaporated. The resulting residue was purified by silica gel column chromatography (methylene chloride/methanol system) and NH-silica gel chromatography (ethyl acetate), to give the free compound of the title compound as a colorless oil (0.71 g, yield; 53.2%).

Workup

  1. customThe reaction solution was partitioned between ethyl acetate and water
  2. washThe organic layer was washed with water
  3. customdried
  4. customevaporated
  5. dissolutionThe resulting residue was dissolved in THF (30 ml)
  6. additionfollowed by the addition of 3M methylmagnesium bromide/ether solution (3.3 ml) under ice-
  7. temperaturecooling
  8. customthe mixture was reacted at room temperature for 1.5 hr
  9. customThe reaction solution was partitioned between ethyl acetate and water
  10. extractionthe aqueous layer was extracted from the organic layer with 2N hydrochloric acid
  11. extractionback-extracted with ethyl acetate
  12. washThe organic layer was washed with water
  13. customdried
  14. customevaporated
  15. customThe resulting residue was purified by silica gel column chromatography (methylene chloride/methanol system) and NH-silica gel chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-9fcec2116d424d3abb0ec950bab0c402
Source dataset
uspto-grants-2005_04
Patent number
US06875761B2

Reaction notes

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