Sodium Carbonate → HCID 66831365, compound

HRID 405994Notes

Reaction equation

HRID 405994 reaction equation
[CH2:1]([C:3]1[NH:4][C:5]2[C:10]([C:11](=[O:14])[C:12]=1I)=[CH:9][C:8]([F:15])=[CH:7][CH:6]=2)[CH3:2].[F:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[C:21]([F:23])[CH:22]=1.C([O-])([O-])=O.[Na+].[Na+]>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>[F:16][C:17]1[CH:18]=[C:19]([C:12]2[C:11](=[O:14])[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([F:15])[CH:9]=3)[NH:4][C:3]=2[CH2:1][CH3:2])[CH:20]=[C:21]([F:23])[CH:22]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 59634716HCID 59634716, compound

Product 1

HCID 66831365HCID 66831365, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A stirred mixture of 2-ethyl-6-fluoroquinolin-4(1H)-one (4.00 g, 21 mmol), I2 (10.62 g, 2.0 eq) and Na2CO3 (3.33 g, 1.5 eq) in THF (100 mL) was stirred at rt overnight. To the reaction mixture was added Na2S2O3 solution, after 2 min the resulted mixture was filtered, washed with water and dried in the air to give a white solid as 2-ethyl-6-fluoro-3-iodoquinolin-4(1H)-one. Mass Spectrum (ESI) m/e=318 (M+1). A mixture of 2-ethyl-6-fluoro-3-iodoquinolin-4(1H)-one (400 mg, 1.3 mmol), 3,5-difluorophenylboronic acid (398 mg, 2.0 eq), Na2CO3 (401 mg, 3.0 eq) and tetrakis(triphenylphosphine)palladium(0) (73 mg, 0.05 eq) in acetonitrile/water (15 mL/5 mL) was purged with N2 and heated to reflux. After overnight, the reaction mixture was cooled at rt, partitioned between water and EtOAc. The layers were separated and the aq layer was extracted with EtOAc (10 mL×2). The combined organic layers were washed with water (10 mL×2), brine (10 mL), dried over Na2SO4, filtered, and concd under reduced pressure. The residue was purified by combiflash on silica gel (EtOAc/DCM, 1:2) to give 3-(3,5-difluorophenyl)-2-ethyl-6-fluoroquinolin-4(1H)-one as a white solid. Mass Spectrum (ESI) m/e=304 (M+1).

Workup

  1. customwas purged with N2
  2. temperatureheated to reflux
  3. custompartitioned between water and EtOAc
  4. customThe layers were separated
  5. extractionthe aq layer was extracted with EtOAc (10 mL×2)
  6. washThe combined organic layers were washed with water (10 mL×2), brine (10 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customThe residue was purified by combiflash on silica gel (EtOAc/DCM, 1:2)

Sources & evidence

ORD record
ord-e0bda731b9a44e339b366ac90346934d
Source dataset
uspto-grants-2014_06
Patent number
US08754089B2

Reaction notes

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