Potassium Carbonate → 5-(4-Fluorophenyl)-3-thiophenecarboxylic acid ethyl ester

HRID 720234Notes

Reaction equation

HRID 720234 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9](Br)[S:8][CH:7]=1)=[O:5])[CH3:2].[F:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].COCCOC.O>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:16]2[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=2)[S:8][CH:7]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 15293216Ethyl 5-bromothiophene-3-carboxylateHCID 18180031Water 1,2-dimethoxyethane

Product 1

HCID 587391355-(4-Fluorophenyl)-3-thiophenecarboxylic acid ethyl esterYield 88.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-bromo-thiophene-3-carboxylic acid ethyl ester (1.0 g, 4.5 mmol), 4-fluorophenylboronic acid (0.88 g. 6.4 mmol), potassium carbonate (1.75 g, 12 mmol) and tetrakistriphenylphosphinepalladium(0) (0.2 g, 4 mole %) in a 50:50 mixture of DME/H2O (10 mL) was heated at reflux temperature overnight under a nitrogen atmosphere. The resulting reaction mixture was cooled, diluted with ethyl acetate and washed with water. The organic layer was washed with brine, dried over sodium sulfate and rotary evaporated. The residue was purified by flash chromatography (silica gel; 2% acetone/hexane) to obtain 5-(4-fluorophenyl)-3-thiophenecarboxylic acid ethyl ester as an oil (1.0 g, 88%). MS: m/z=251 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature overnight under a nitrogen atmosphere
  3. customThe resulting reaction mixture
  4. temperaturewas cooled
  5. washwashed with water
  6. washThe organic layer was washed with brine
  7. dry with materialdried over sodium sulfate and rotary evaporated
  8. customThe residue was purified by flash chromatography (silica gel; 2% acetone/hexane)

Sources & evidence

ORD record
ord-cbc21121cf174e21ab8e77a2e1ecdc13
Source dataset
uspto-grants-2006_11
Patent number
US07135470B2

Reaction notes

Loading…