Methyl 5-bromothiophene-2-carboxylate → Methyl 5-(3-tert-butyl-4-methoxyphenyl)-2-thiophenecarboxylate

HRID 2417315Notes

Reaction equation

HRID 2417315 reaction equation
[C:1]([C:5]1[CH:6]=[C:7](Br)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12])([CH3:4])([CH3:3])[CH3:2].[Mg].Br[C:16]1[S:20][C:19]([C:21]([O:23][CH3:24])=[O:22])=[CH:18][CH:17]=1>C1COCC1.[Cl-].[Zn+2].[Cl-]>[C:1]([C:5]1[CH:6]=[C:7]([C:16]2[S:20][C:19]([C:21]([O:23][CH3:24])=[O:22])=[CH:18][CH:17]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 605713Methyl 5-bromothiophene-2-carboxylateHCID 3733898LABOTEST-BB LT00239243HCID 5462224Magnesium

Product 1

HCID 15382605Methyl 5-(3-tert-butyl-4-methoxyphenyl)-2-thiophenecarboxylate

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2 g (8.2 mmol) of 3-tert-butyl-4-methoxybromobenzene is added dropwise to a suspension of 300 mg (12 mmol) of magnesium in 10 ml of THF. Once the addition is complete, the mixture is refluxed for one hour. At room temperature, 1.35 g (9.9 mmol) of anhydrous zinc chloride are added and the mixture is stirred for one hour. 1.2 g (5.5 mmol) of methyl 5-bromo-2-thiophenecarboxylate and 60 mg (0.12 mmol) of the NiCl2/DPPE complex are then added successively and the mixture is left stirring at room temperature for 12 hours. The reaction medium is poured into ice-water and extracted with ethyl ether and the organic phase is separated out after settling has taken place, dried over magnesium sulphate and evaporated. The residue obtained is chromatographed on a column of silica eluted with a mixture of hexane and dichloromethane (50/50% by volume). After evaporation of the solvents, 1.56 g (93%) of the expected methyl ester are collected, with a melting point of 94-5° C.

Workup

  1. additionOnce the addition
  2. temperaturethe mixture is refluxed for one hour
  3. waitthe mixture is left
  4. stirringstirring at room temperature for 12 hours
  5. extractionextracted with ethyl ether
  6. customthe organic phase is separated out after settling
  7. dry with materialdried over magnesium sulphate
  8. customevaporated
  9. customThe residue obtained
  10. customis chromatographed on a column of silica
  11. washeluted with a mixture of hexane and dichloromethane (50/50% by volume)
  12. customAfter evaporation of the solvents, 1.56 g (93%) of the expected methyl ester
  13. customare collected, with a melting point of 94-5° C.

Sources & evidence

ORD record
ord-c683eb7587ae411e9933cde239ecae4f
Source dataset
uspto-grants-2004_11
Patent number
US06825360B1

Reaction notes

Loading…