Ethyl Acetate → 1-[3-(5-Chloro-thiophen-2-yl)-4-fluoro-phenyl]-ethanone

HRID 1098765Notes

Reaction equation

HRID 1098765 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][C:3]=1B(O)O.Br[C:15]1[S:16][C:17]([Cl:20])=[CH:18][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>C(#N)C.O.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>[Cl:20][C:17]1[S:16][C:15]([C:3]2[CH:4]=[C:5]([C:8](=[O:10])[CH3:9])[CH:6]=[CH:7][C:2]=2[F:1])=[CH:19][CH:18]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 761332-Bromo-5-chlorothiopheneHCID 27632475-Acetyl-2-fluorobenzeneboronic acid

Product 1

HCID 595062311-[3-(5-Chloro-thiophen-2-yl)-4-fluoro-phenyl]-ethanoneYield 42.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-fluoro-5-acetylphenylboronic acid (5.00 g, 27.48 mmol) in ACN (80 mL) and H2O (20 mL) were added 2-bromo-5-chlorothiophene (5.43 g, 27.48 mmol), sodium carbonate (2.91 g, 27.48 mmol) and tetrakis(triphenylphosphine)palladium(0) (635 mg, 0.02 mmol). The reaction mixture was refluxed for 3 h. After cooling, ethyl acetate (150 ml) and water (150 ml) were added. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over sodium sulfate. Evaporation and purification of the crude product by silica gel chromatography using ethyl acetate/heptane gave the desired product (2.95 g, 42%).

Workup

  1. temperatureThe reaction mixture was refluxed for 3 h
  2. temperatureAfter cooling
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. customEvaporation and purification of the crude product by silica gel chromatography

Sources & evidence

ORD record
ord-a83551781863409a8a53021e3001572d
Source dataset
uspto-grants-2012_03
Patent number
US08143242B2

Reaction notes

Loading…