Ethanol → HCID 15887920, compound

HRID 377288Notes

Reaction equation

HRID 377288 reaction equation
Br[C:2]1[C:11]([O:12][CH:13]([F:15])[F:14])=[C:10]2[C:5]([C:6](=[O:24])[C:7]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:8][N:9]2[CH:16]2[CH2:18][CH2:17]2)=[CH:4][CH:3]=1.C(O)C.C(=O)([O-])[O-].[Na+].[Na+].[CH3:34][CH:35]1[C:43]2[C:38](=[CH:39][C:40](B(O)O)=[CH:41][CH:42]=2)[CH2:37][N:36]1[C:47]([C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)([C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.C(OCC)(=O)C>[CH:16]1([N:9]2[C:10]3[C:5](=[CH:4][CH:3]=[C:2]([C:40]4[CH:39]=[C:38]5[C:43](=[CH:42][CH:41]=4)[CH:35]([CH3:34])[N:36]([C:47]([C:60]4[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=4)([C:54]4[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=4)[C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)[CH2:37]5)[C:11]=3[O:12][CH:13]([F:15])[F:14])[C:6](=[O:24])[C:7]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:8]2)[CH2:18][CH2:17]1

Participants

9

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 11732152Ethyl 7-bromo-1-cyclopropyl-8-(difluoromethoxy)-4-oxo-1,4-dihydroquinoline-3-carboxylateHCID 18401805HCID 18401805, compound

Product 1

HCID 15887920HCID 15887920, compoundYield 59.4%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 7 ml of toluene was suspended 0.70 g of ethyl 7-bromo-1-cyclopropyl-8-difluoromethoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate, followed by adding thereto 3 ml of ethanol, 1.74 ml of a 2 M aqueous sodium carbonate solution, 0.80 g of (+)-1-methyl-2-trityliso-indoline-5-boronic acid and 0.05 g of bis(triphenyl-phosphine)palladium(II) chloride, and the resulting mixture was heated under reflux for 2 hours under a nitrogen atmosphere. The reaction mixture was added to a mixed solvent of 10 ml of ethyl acetate and 10 ml of water, and the organic layer was separated. The organic layer obtained was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to remove the solvent. The resulting residue was purified by a column chromatography (eluent; n-hexane:ethyl acetate=1:1) to obtain 0.72 g of ethyl (+)-1-cyclopropyl-8-difluoromethoxy-7-(1-methyl-2-trityliso-indolin-5-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylate as colorless crystals.

Workup

  1. additionby adding
  2. temperatureunder reflux for 2 hours under a nitrogen atmosphere
  3. customthe organic layer was separated
  4. customThe organic layer obtained
  5. washwas washed with a saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationdistilled under reduced pressure
  8. customto remove the solvent
  9. customThe resulting residue was purified by a column chromatography (eluent; n-hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-19537fe02ebd4bd995f4404c3578523d
Source dataset
uspto-grants-2000_02
Patent number
US06025370

Reaction notes

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