Ethyl 6-chloro-2-(chloromethyl)-4-phenyl-3-quinolinecarboxylate → Ethyl 6-chloro-2-((1,3-dioxoisoindolin-2-yl)methyl)-4-phenylquinoline-3-carboxylate

HRID 538745Notes

Reaction equation

HRID 538745 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12]Cl)[C:6]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:5]2[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[C:25]1(=[O:35])[NH:29][C:28](=[O:30])[C:27]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:26]12.[K]>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][N:29]1[C:25](=[O:35])[C:26]3[C:27](=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:28]1=[O:30])[C:6]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:5]2[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 2

HCID 14417743Ethyl 6-chloro-2-(chloromethyl)-4-phenyl-3-quinolinecarboxylateHCID 24194345Phthalimide potassium salt

Product 1

HCID 46214748Ethyl 6-chloro-2-((1,3-dioxoisoindolin-2-yl)methyl)-4-phenylquinoline-3-carboxylateYield 82.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of ethyl 6-chloro-2-(chloromethyl)-4-phenylquinoline-3-carboxylate (539 mg, 1.5 mmol) in dry N,N-dimethylformamide (5 ml) at room temperature was added potassium phthalimide (278 mg, 1.5 mmol). The mixture was heated at 45° C. for 48 hours, then diluted with ethyl acetate and poured into a separatory funnel. The organic phase was washed with saturated sodium bicarbonate, water (2×), then brine. The organic phase was separated, and the solvent removed under reduced pressure, leaving a white solid, which was washed with a cold solution of 10% diethylether/hexanes, dried under reduced pressure, to provide ethyl 6-chloro-2-((1,3-dioxoisoindolin-2-yl)methyl)-4-phenylquinoline-3-carboxylate (580 mg, 82%) as a white powder. TLC Rf=0.41 using 1:1 ethyl acetate:hexanes eluent on a glass backed silica gel plate. 1H NMR (CDCl3, 400 MHz) δ 7.98 (m, 2H); 7.78 (m, 3H); 7.58 (m, 5H); 7.38 (m, 2H); 5.30 (s, 2H); 4.04 (q, 2H, J=7.0 Hz); 0.89 (t, 3H, J=7.0 Hz). LC MS (CI) shows M+H 471.

Workup

  1. additionpoured into a separatory funnel
  2. washThe organic phase was washed with saturated sodium bicarbonate, water (2×)
  3. customThe organic phase was separated
  4. customthe solvent removed under reduced pressure
  5. customleaving a white solid, which
  6. washwas washed with a cold solution of 10% diethylether/hexanes
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-23f539cc52ef48179f5c2f2010541763
Source dataset
uspto-grants-2014_10
Patent number
US08865739B2

Reaction notes

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