Cesium acetate → acetoxymethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 2046157Notes

Reaction equation

HRID 2046157 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:29]=[C:28]3[C:23]([CH2:24][CH2:25][C:26](=[O:35])[N:27]3[C:30]([O:32][CH2:33]Cl)=[O:31])=[CH:22][CH:21]=2)[CH2:11][CH2:10]1.[C:36]([O-:39])(=[O:38])[CH3:37].[Cs+]>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:29]=[C:28]3[C:23]([CH2:24][CH2:25][C:26](=[O:35])[N:27]3[C:30]([O:32][CH2:33][O:38][C:36](=[O:39])[CH3:37])=[O:31])=[CH:22][CH:21]=2)[CH2:13][CH2:14]1

Participants

5

Reactant 2

HCID 5152919Cesium acetateHCID 66810238chloromethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 56597051acetoxymethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of chloromethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate (1.20 g, 2.22 mmol) in dimethyl formamide (20 mL) was added cesium acetate (639 mg, 3.33 mmol). The reaction was then stirred at ambient temperature overnight. The reaction was diluted with ethyl acetate (50 mL) and quenched with water/brine (1:1, 50 mL). The reaction was extracted with ethyl acetate (3×50 mL). The combined organics were washed with water (50 mL) then brine (50 mL) and dried (MgSO4) and concentrated. The crude product was purified by column chromatography on silica eluting with 0-10% tetrahydrofuran/dichloromethane with 1% Et3N to give the product which required further purification. The product was purified by column chromatography on silica eluting with 0.5% Et3N/ethyl acetate to give acetoxymethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate, Compound-87 (243 mg, 19% over 2 steps).

Workup

  1. customquenched with water/brine (1:1, 50 mL)
  2. extractionThe reaction was extracted with ethyl acetate (3×50 mL)
  3. washThe combined organics were washed with water (50 mL)
  4. dry with materialbrine (50 mL) and dried (MgSO4)
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography on silica eluting with 0-10% tetrahydrofuran/dichloromethane with 1% Et3N
  7. customto give the product which
  8. custompurification
  9. customThe product was purified by column chromatography on silica eluting with 0.5% Et3N/ethyl acetate

Sources & evidence

ORD record
ord-587441d6ca97413abdc7d8e97c9c583a
Source dataset
uspto-grants-2013_11
Patent number
US08592427B2

Reaction notes

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