Sodium Hydroxide → Ethyl 4-bromo-3-methylthiophene-2-carboxylate

HRID 1386123Notes

Reaction equation

HRID 1386123 reaction equation
[CH3:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].[OH-].[Na+].[Br:14]Br>C(O)(=O)C.[Zn]>[Br:14][C:6]1[C:2]([CH3:1])=[C:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[S:4][CH:5]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 24408BromineHCID 18347931Ethyl 3-methylthiophene-2-carboxylate

Product 1

HCID 18347936Ethyl 4-bromo-3-methylthiophene-2-carboxylateYield 97%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
85 °C

Procedure

A solution of ethyl 3-methyl-2-thiophenecarboxylate (20.0 g, 0.118 mol) and sodium hydroxide (12.3 g, 0.307 mol) in acetic acid (75 mL) was heated to 60° C. Bromine (46.9 g, 0.294 mol) was added dropwise at such a rate so as to maintain the temperature of the reaction mixture at <85° C. When the addition was complete, the resulting solution was stirred at 85° C. for 6 hours, at which time analysis by gas chromatography/mass spectrometry showed complete conversion to ethyl 4,5-dibromo-3-methyl-2-thophenecarboxylate. The solution was allowed to cool to 50° C. and zinc dust (15.4 g, 0.236 mol) was added in 3 gram portions such that the exotherm was controlled to remain below 85° C. When the addition was completed, the resulting slurry was stirred at 85° C. for one hour. The solution was filtered hot through a small bed of celite. Water (300 mL) was added and the mixture was extracted with heptanes (300 mL). The organic phase was washed with water, then concetrated to dryness to give 26.9 g (89%) as an off white oil which slowly crystallized upon standing at ambient temperature. In a similar fashion, methyl 3-methyl-2-thiophenecarboxylate may be converted methyl-4bromo-3-methyl-2-thiophenecarboxyltate in 97% yield.

Workup

  1. temperatureto maintain the temperature of the reaction mixture at <85° C
  2. additionWhen the addition
  3. temperatureto cool to 50° C.
  4. customto remain below 85° C
  5. additionWhen the addition
  6. stirringthe resulting slurry was stirred at 85° C. for one hour
  7. filtrationThe solution was filtered hot through a small bed of celite
  8. additionWater (300 mL) was added
  9. extractionthe mixture was extracted with heptanes (300 mL)
  10. washThe organic phase was washed with water
  11. customto give 26.9 g (89%) as an off white oil which
  12. customslowly crystallized
  13. customupon standing at ambient temperature

Sources & evidence

ORD record
ord-f26a23e5ad244cd49e25a95e883bab31
Source dataset
uspto-grants-2001_07
Patent number
US06265424B1

Reaction notes

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