Sodium Carbonate → Ethyl 1-cyclopropyl-8-(difluoromethoxy)-7-[(1R)-2,3-dihydro-1-methyl-2-(triphenylmethyl)-1H-isoindol-5-yl]-1,4-dihydro-4-oxo-3-quinolinecarboxylate

HRID 2222861Notes

Reaction equation

HRID 2222861 reaction equation
[CH3:1][C@@H:2]1[C:10]2[C:5](=[CH:6][C:7](B3OCCNCCO3)=[CH:8][CH:9]=2)[CH2:4][N:3]1[C:19]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Br[C:39]1[C:48]([O:49][CH:50]([F:52])[F:51])=[C:47]2[C:42]([C:43](=[O:61])[C:44]([C:56]([O:58][CH2:59][CH3:60])=[O:57])=[CH:45][N:46]2[CH:53]2[CH2:55][CH2:54]2)=[CH:41][CH:40]=1.C(=O)([O-])[O-].[Na+].[Na+]>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(Cl)Cl.C(OCC)(=O)C>[CH:53]1([N:46]2[C:47]3[C:42](=[CH:41][CH:40]=[C:39]([C:7]4[CH:6]=[C:5]5[C:10](=[CH:9][CH:8]=4)[C@@H:2]([CH3:1])[N:3]([C:19]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:4]5)[C:48]=3[O:49][CH:50]([F:52])[F:51])[C:43](=[O:61])[C:44]([C:56]([O:58][CH2:59][CH3:60])=[O:57])=[CH:45]2)[CH2:55][CH2:54]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 104131955-(1,3,6,2-Dioxazaborocan-2-yl)-1-methyl-2-(triphenylmethyl)-2,3-dihydro-1H-isoindoleHCID 11732152Ethyl 7-bromo-1-cyclopropyl-8-(difluoromethoxy)-4-oxo-1,4-dihydroquinoline-3-carboxylate

Product 1

HCID 15887919Ethyl 1-cyclopropyl-8-(difluoromethoxy)-7-[(1R)-2,3-dihydro-1-methyl-2-(triphenylmethyl)-1H-isoindol-5-yl]-1,4-dihydro-4-oxo-3-quinolinecarboxylateYield 89.5%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a mixed solvent of 2 ml of water and 5 ml of ethyl acetate is suspended 1.34 g of 2-[(1R)-1-methyl-2-trityl-2,3-dihydro-1H-5-isoindolyl]-1,3,6,2-dioxazaborocane and to this suspension are added 1.0 g of ethyl 7-bromo-1-cyclopropyl-8-difluoromethoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate, 0.55 g of sodium carbonate and 0.05 g of bis(triphenylphosphine)palladium(II) chloride, after which the resulting mixture is heated under reflux for 3 hours in a nitrogen atmosphere. The reaction mixture is added to a mixed solvent of 10 ml of methylene chloride and 10 ml of water and the organic layer is separated. The organic layer obtained is washed with saturated saline and then dried over anhydrous magnesium sulfate, after which the solvent is removed from the layer by distillation under reduced pressure. The residue obtained is recrystallized from ethanol to obtain 1.55 g of ethyl 1-cyclopropyl-8-difluoromethoxy-7-[(1R)-1-methyl-2-trityl-2,3-dihydro-1H-5-isoindolyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylate.

Workup

  1. temperatureafter which the resulting mixture is heated
  2. temperatureunder reflux for 3 hours in a nitrogen atmosphere
  3. customthe organic layer is separated
  4. customThe organic layer obtained
  5. washis washed with saturated saline
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customafter which the solvent is removed from the layer by distillation under reduced pressure
  8. customThe residue obtained
  9. customis recrystallized from ethanol

Sources & evidence

ORD record
ord-be64444d2e004715a2a5a1ac8a9caeef
Source dataset
uspto-grants-2008_05
Patent number
US07371868B2

Reaction notes

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