Water → Ethyl 4-bromothiophene-3-carboxylate

HRID 552090Notes

Reaction equation

HRID 552090 reaction equation
Br[C:2]1[C:6]([Br:7])=[CH:5][S:4][CH:3]=1.C([Mg]Cl)(C)C.Cl[C:14]([O:16][CH2:17][CH3:18])=[O:15].O>O1CCCC1>[CH2:17]([O:16][C:14]([C:2]1[C:6]([Br:7])=[CH:5][S:4][CH:3]=1)=[O:15])[CH3:18]

Participants

6

Reactant 4

HCID 962WaterHCID 10928Ethyl chloroformateHCID 184523,4-DibromothiopheneHCID 178418918HCID 178418918, compound

Product 1

HCID 57455182Ethyl 4-bromothiophene-3-carboxylateYield 98.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
2.5 °C

Procedure

To a 0° C. solution of 3,4-dibromothiophene (1.0 Kg, 4.13 mol) in tetrahydrofuran (7.4 Kg) was added iPrMgCl (2.0 M solution in tetrahydrofuran, 2.58 Kg, 5.17 mol) keeping the temperature below 5° C. The resulting mixture was stirred at 0-5° C. for 5 hours. To the cooled Grignard solution was added ethyl chloroformate (896 g, 5.17 mol) dropwise keeping the temperature below 10° C. The resulting mixture was warmed to room temperature, and stirred for 16 hours. Water (200 mL) was added to the reaction mixture, and the resulting mixture was stirred at room temperature for 10 min. The majority of the tetrahydrofuran was then removed under vacuum and ethyl acetate (4.5 Kg) was added to the mixture followed by 1N aqueous hydrochloric acid. The layers were separated, and the organic layer was washed with 12% brine (5.0 Kg). The solvent was removed under vacuum to give a yellow oil, which was filtered to remove salts to provide 956 g (98% yield) of 4-bromo-thiophene-3-carboxylic acid ethyl ester, which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3): δ 8.10 (d, 1H, J=3.5 Hz), 7.30 (d, 1H, J=3.6 Hz), 4.34 (q, 2H, J=7.10 Hz), 1.38 (t, 3H, J=7.20 Hz); 13C NMR (400 MHz, CDCl3): δ 14.49, 60.95, 110.49, 124.86, 130.93, 133.67, 160.68.

Workup

  1. customthe temperature below 5° C
  2. customthe temperature below 10° C
  3. temperatureThe resulting mixture was warmed to room temperature
  4. stirringstirred for 16 hours
  5. stirringthe resulting mixture was stirred at room temperature for 10 min
  6. customThe majority of the tetrahydrofuran was then removed under vacuum and ethyl acetate (4.5 Kg)
  7. additionwas added to the mixture
  8. customThe layers were separated
  9. washthe organic layer was washed with 12% brine (5.0 Kg)
  10. customThe solvent was removed under vacuum
  11. customto give a yellow oil, which
  12. filtrationwas filtered
  13. customto remove salts

Sources & evidence

ORD record
ord-38ac3671504e4c308933e8efc46b4e96
Source dataset
uspto-grants-2011_05
Patent number
US07951800B2

Reaction notes

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