Water → 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 1018528Notes

Reaction equation

HRID 1018528 reaction equation
O.[CH3:2][C@@H:3]1[C:11]2[C:6](=[CH:7][C:8](B3OCCNCCO3)=[CH:9][CH:10]=2)[CH2:5][N:4]1[C:20]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Br[C:40]1[C:49]([O:50][CH:51]([F:53])[F:52])=[C:48]2[C:43]([C:44](=[O:62])[C:45]([C:57]([O:59][CH2:60][CH3:61])=[O:58])=[CH:46][N:47]2[CH:54]2[CH2:56][CH2:55]2)=[CH:42][CH:41]=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.C(O)C.C(O)(=O)C.COCCOCCOC>[CH:54]1([N:47]2[C:48]3[C:43](=[CH:42][CH:41]=[C:40]([C:8]4[CH:7]=[C:6]5[C:11](=[CH:10][CH:9]=4)[C@@H:3]([CH3:2])[N:4]([C:20]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)[C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:5]5)[C:49]=3[O:50][CH:51]([F:53])[F:52])[C:44](=[O:62])[C:45]([C:57]([O:59][CH2:60][CH3:61])=[O:58])=[CH:46]2)[CH2:56][CH2:55]1

Participants

9

Reactant 4

HCID 962WaterHCID 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 98.9%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 8150DiglymeSolvent

Conditions

Temperature
40 °C

Procedure

In a mixed solvent of 50.6 ml of water and 50.6 ml of diethylene glycol dimethyl ether is suspended 13.5 g of 2-[(1R)-1-methyl-2-trityl-2,3-dihydro-1H-5-isoindolyl]-1,3,6,2-dioxazaborocane and to this suspension is added 1.58 ml of acetic acid, after which the resulting mixture is stirred for 30 minutes. To this mixture are further added 10.1 g of ethyl 7-bromo-1-cyclopropyl-8-difluoromethoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate, 5.59 g of sodium carbonate and 0.088 g of bis(triphenylphosphine)-palladium(II) chloride, and the resulting mixture is heated under reflux for 2 hours in a nitrogen atmosphere. The reaction mixture is cooled to 40° C. and thereafter the organic layer is separated. To the organic layer obtained is added 30 ml of ethanol and the crystals deposited are collected by filtration to obtain 17.3 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. The physical property values of this compound were identical with those of the compound obtained in Production Example II-1.

Workup

  1. temperaturethe resulting mixture is heated
  2. temperatureunder reflux for 2 hours in a nitrogen atmosphere
  3. customthe organic layer is separated
  4. customTo the organic layer obtained
  5. filtrationthe crystals deposited are collected by filtration

Sources & evidence

ORD record
ord-41d530ef640345b3a84adc81f2c9280c
Source dataset
uspto-grants-2002_11
Patent number
US06482835B2

Reaction notes

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