HCID 11427516, compound → HCID 19081600, compound

HRID 963387Notes

Reaction equation

HRID 963387 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:12]2[O:17][CH2:16][C:15]([CH3:19])([CH3:18])[CH2:14][O:13]2)[CH:5]=[C:6]([O:10][CH3:11])[C:7]=1[O:8][CH3:9].C([Li])CCC.[CH:25]1([N:28]2[C:37]3[C:32](=[CH:33][C:34]([F:46])=[C:35](OS(C(F)(F)F)(=O)=O)[CH:36]=3)[C:31](=[O:47])[C:30]([C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:29]2)[CH2:27][CH2:26]1>O1CCCC1.CCCCCC.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH:25]1([N:28]2[C:37]3[C:32](=[CH:33][C:34]([F:46])=[C:35]([C:2]4[CH:3]=[C:4]([CH:12]5[O:17][CH2:16][C:15]([CH3:19])([CH3:18])[CH2:14][O:13]5)[CH:5]=[C:6]([O:10][CH3:11])[C:7]=4[O:8][CH3:9])[CH:36]=3)[C:31](=[O:47])[C:30]([C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:29]2)[CH2:26][CH2:27]1

Participants

8

Reactant 3

HCID 11427516HCID 11427516, compoundHCID 15636882HCID 15636882, compoundHCID 178418339Butyllithium

Product 1

HCID 19081600HCID 19081600, compoundYield 68.5%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.17 g of 2-(3-bromo-4,5-dimethoxy-phenyl)-5,5-dimethyl-1,3-dioxan (Example 6a)) in 10 ml of tetrahydrofuran is treated dropwise at -100° over 20 minutes with 2.2 ml of a 1.6M n-butyllithium solution in n-hexane. The solution is stirred for a further hour at -100° and then treated dropwise at this temperature with 7 ml of a 0.5M zinc chloride solution in tetrahydrofuran within 20 minutes. The reaction mixture is warmed slowly to 0° and stirred at this temperature for a further 1hr. The solution is then slowly added dropwise through a Teflon tube to a boiling mixture of 1 g of ethyl 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[[(trifluoromethyl)sulphonyl]oxy]quinoline-3-carboxylate (J. Heterocyclic Chem., 28, 1581 (1991)) and 20 mg of tetrakis-triphenylphosphine-palladium in 10 ml of tetrahydrofuran. The mixture is stirred at reflux temperature for a further 2 hrs. it is cooled to room temperature, diluted with 50 ml of ethyl acetate and washed with 50 ml of a saturated aqueous ammonium chloride solution, 50 ml of water and 50 ml of a saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate and concentrated. The residue is chromatographed on silica gel with ethyl acetate. 850 mg (68%) of ethyl 1-cyclopropyl-7-[5-(5,5-dimethyl-1,3-dioxan-2-yl)-2,3-dimethoxy-phenyl]-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate are isolated as a colourless solid. M.p. 178°-180° after recrystallization from ethyl acetate/n-hexane.

Workup

  1. temperatureThe reaction mixture is warmed slowly to 0°
  2. stirringstirred at this temperature for a further 1hr
  3. stirringThe mixture is stirred
  4. temperatureat reflux temperature for a further 2 hrs
  5. washwashed with 50 ml of a saturated aqueous ammonium chloride solution, 50 ml of water and 50 ml of a saturated aqueous sodium chloride solution
  6. dry with materialThe organic phase is dried over magnesium sulphate
  7. concentrationconcentrated
  8. customThe residue is chromatographed on silica gel with ethyl acetate

Sources & evidence

ORD record
ord-ae5a0e4aa55e41598fc9be7b1745f786
Source dataset
uspto-grants-1998_06
Patent number
US05763450

Reaction notes

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