Butyric Acid → butyryloxymethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 2046158Notes

Reaction equation

HRID 2046158 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]([OH:41])(=[O:40])[CH2:37][CH2:38][CH3:39].C(=O)([O-])[O-].[Cs+].[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:41][C:36](=[O:40])[CH2:37][CH2:38][CH3:39])=[O:31])=[CH:22][CH:21]=2)[CH2:13][CH2:14]1

Participants

6

Reactant 3

HCID 264Butyric AcidHCID 10796Cesium carbonateHCID 66810238chloromethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 56597052butyryloxymethyl 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 butyric acid (0.30 mL, 3.33 mmol) followed by cesium carbonate (542 mg, 1.67 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 010% tetrahydrofuran/dichloromethane with 1% Et3N to give the product which required further purification. The product was purified by column chromatography on silica eluting with 0.51.5% Et3N/ethyl acetate to give butyryloxymethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate, Compound-88 (348 mg, 26% 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 010% 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

Sources & evidence

ORD record
ord-fac0fbff60b142f19dbb692889279d51
Source dataset
uspto-grants-2013_11
Patent number
US08592427B2

Reaction notes

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