Water → Dimethyl 7-chloroquinoline-2,3-dicarboxylate

HRID 1449564

Reaction equation

HRID 1449564 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]([O:15][CH3:16])=[O:14])[C:3]=1[C:17]([O:19][CH3:20])=[O:18].C([O-])=O.[Na+].O>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[Cl:12][C:8]1[CH:7]=[C:6]2[C:11]([CH:2]=[C:3]([C:17]([O:19][CH3:20])=[O:18])[C:4]([C:13]([O:15][CH3:16])=[O:14])=[N:5]2)=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 962WaterHCID 2723810Sodium FormateHCID 18929951Dimethyl 4,7-dichloroquinoline-2,3-dicarboxylate

Product 1

HCID 18929843Dimethyl 7-chloroquinoline-2,3-dicarboxylateYield 134.8%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A stirred mixture of dimethyl 4,7-dichloroquinoline-2,3-dicarboxylate (5.00 g, 15.9 mM), sodium formate (1.63 g, 23.9 mM) and tetrakis(triphenylphosphine)palladium(O) (0.92 g, 0.80 mM) in anhydrous dimethylformamide (75 mL) under a nitrogen atmosphere was heated at 90°-95° C. for 7 hr. No reaction occurred so the reaction mixture was degassed and an additional quantity of tetrakis(triphenylphosphine)palladium(O) (0.92 g, 0.80 mM) was added and the reaction mixture again heated at 90°-95° C. for 6 hr. The cooled reaction mixture was poured into water and the resulting mixture extracted with ethyl acetate. The combined extracts were dried (MgSO4), filtered and concentrated to leave an gummy solid (6.0 g). Trituration of this residue with ethyl acetate and subsequent filtration separated a crystalline solid which was shown to be dimethyl 7-chloro-4-hydroxyquinoline-2,3-dicarboxylate. The filtrate was concentrated and the residue was flash chromatographed over silica gel (eluant: hexane/ethyl acetate, 3/2) to provide the title diester (1.13 g, 25.4%) as a light yellow crystalline solid; MS(CI): 280 (M+H). 300-MHz 1H NMR (DMSO d6), 9.15 (s, 1H), 8.33 (d, 1H, J=9 Hz), 8.25 (d, 1H, J=2 Hz), 7.86 (dd, 1H, J=9 Hz, 2 Hz), 3.93 (s, 3H), 3.92 (s, 3H).

Workup

  1. temperaturewas heated at 90°-95° C. for 7 hr
  2. customwas degassed
  3. additionan additional quantity of tetrakis(triphenylphosphine)palladium(O) (0.92 g, 0.80 mM) was added
  4. temperaturethe reaction mixture again heated at 90°-95° C. for 6 hr
  5. customThe cooled reaction mixture
  6. extractionthe resulting mixture extracted with ethyl acetate
  7. dry with materialThe combined extracts were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-f6907b34b0c342fcb7ba55f380ddb031
Source dataset
uspto-grants-1997_02
Patent number
US05599814

Linked notes

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