2-Fluoroaniline → N-((8-fluoro-2-phenylquinolin-3-yl)methyl)acetamide

HRID 216814Notes

Reaction equation

HRID 216814 reaction equation
[N:1]1([C:5](=[O:7])[CH3:6])[CH:4]=[CH:3][CH2:2]1.[CH:8](=[N:15]/[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[F:22])\[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.FC1C=CC=CC=1N>C(#N)C.FC(F)(F)S([O-])(=O)=O.[Y+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>[F:22][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[C:16]=1[N:15]=[C:8]([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:3]([CH2:2][NH:1][C:5](=[O:7])[CH3:6])=[CH:4]2

Participants

6

Reactant 3

HCID 95842-FluoroanilineHCID 109094921-Acetyl-1,2-dihydroazeteHCID 178505640HCID 178505640, compound

Product 1

HCID 57708035N-((8-fluoro-2-phenylquinolin-3-yl)methyl)acetamide

Reagents, catalysts & solvents 2

HCID 2733939Yttrium trifluoromethanesulfonateCatalystHCID 6342AcetonitrileSolvent

Procedure

Dissolved 1-(azet-1(2H)-yl)ethanone (22 mg, 227 μmol, 1 eq), (E)-N-benzylidene-2-fluorobenzenamine (45 mg, 227 μmol, 1 eq), 2-fluorobenzenamine (22 μl, 227 μmol, 1 eq), and yttrium trifluoromethanesulfonate (6 mg, 11 μmol, 0.05 eq) in 9 mL of acetonitrile. The reaction was stirred at rt overnight. The reaction was heated to 90° C. for 5 h. The reaction was cooled to rt and the solvent was removed under vacuum. The residue was dissolved in 20 mL of DCM and washed with 1×5 mL of NaHCO3. The organic layer was dried over MgSO4, filtered and concentrated. Purification by column chromatography (7:3 hexanes:ethyl acetate) afforded N-((8-fluoro-2-phenylquinolin-3-yl)methyl)acetamide. 1H NMR (400 MHz, CDCl3) δ ppm 8.20 (s, 1H), 7.60 (d, J=7.83, 1H), 7.50 (m, 2H), 7.45 (m, 4H), 7.37 (ddd, J=10.6, 7.8, 1.6 Hz, 1H), 5.92 (br t, J=5.9 Hz, 1H), 4.55 (d, J=6.3 Hz, 2H), 1.96 (s, 3H). Mass Spectrum (ESI) m/e=295.0 (M+1).

Workup

  1. temperatureThe reaction was heated to 90° C. for 5 h
  2. temperatureThe reaction was cooled to rt
  3. customthe solvent was removed under vacuum
  4. dissolutionThe residue was dissolved in 20 mL of DCM
  5. washwashed with 1×5 mL of NaHCO3
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by column chromatography (7:3 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-326cabe210e843e398b2dea031ce48b1
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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