7-Acetyl-5-fluoroquinolin-8-yl trifluoromethanesulfonate → 1-[5-Fluoro-8-(3-fluorophenyl)quinolin-7-yl]ethanone

HRID 1192690Notes

Reaction equation

HRID 1192690 reaction equation
FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([F:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.[F:23][C:24]1[CH:25]=[C:26]([Zn]I)[CH:27]=[CH:28][CH:29]=1>O1CCCC1.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>[F:17][C:10]1[CH:9]=[C:8]([C:18](=[O:20])[CH3:19])[C:7]([C:28]2[CH:27]=[CH:26][CH:25]=[C:24]([F:23])[CH:29]=2)=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2

Participants

5

Reactant 2

HCID 583685787-Acetyl-5-fluoroquinolin-8-yl trifluoromethanesulfonateHCID 178505804HCID 178505804, compound

Product 1

HCID 583684731-[5-Fluoro-8-(3-fluorophenyl)quinolin-7-yl]ethanoneYield 11%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

A mixture of 7-acetyl-5-fluoroquinolin-8-yl trifluoromethanesulfonate (3.4 g, 10. mmol, from Example 53, Step 2) in tetrahydrofuran (10 mL) was degassed for 10 minutes, to which was added tetrakis(triphenylphosphine)palladium(0) (1.2 g, 1.0 mmol) and 0.5 M (3-fluorophenyl)(iodo)zinc in tetrahydrofuran (50 mL). The reaction mixture was heated at 65° C. overnight, and then cooled to room temperature. The reaction was quenched with sat. NaHCO3 solution. The mixture was filtered through a Celite pad. The filtrate was extracted with dichloromethane. The combined organic layers were wash with brine, dried over MgSO4, concentrated and purified on silica gel (eluting with 0 to 30% ethyl acetate in hexane) to give the desired product (0.32 g, 11%). LCMS calculated for C17H12F2NO (M+H)+: m/z=284.1; Found: 284.1.

Workup

  1. customwas degassed for 10 minutes, to which
  2. temperaturecooled to room temperature
  3. customThe reaction was quenched with sat. NaHCO3 solution
  4. filtrationThe mixture was filtered through a Celite pad
  5. extractionThe filtrate was extracted with dichloromethane
  6. washThe combined organic layers were wash with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. custompurified on silica gel (eluting with 0 to 30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-7c6bdce6a9c24b05ab3179c2ea46b5e6
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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