Water → HCID 68432514, compound

HRID 1018532Notes

Reaction equation

HRID 1018532 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:18]4[CH:19]=[C:20]5[C:24](=[CH:25][CH:26]=4)[C@@H:23]([CH3:27])[N:22](C(=O)C(C)(C)C)[CH2:21]5)[C:12]=3[O:14][CH:15]([F:17])[F:16])[C:7](=[O:34])[C:6]([C:35]([O:37]CC)=[O:36])=[CH:5]2)[CH2:3][CH2:2]1.O>Cl>[OH2:14].[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:18]4[CH:19]=[C:20]5[C:24](=[CH:25][CH:26]=4)[C@@H:23]([CH3:27])[NH:22][CH2:21]5)[C:12]=3[O:14][CH:15]([F:17])[F:16])[C:7](=[O:34])[C:6]([C:35]([OH:37])=[O:36])=[CH:5]2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 962WaterHCID 15887918HCID 15887918, compound

Product 1

HCID 68432514HCID 68432514, compoundYield 182.1%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

In 68 ml of conc. hydrochloric acid is suspended 34 g of ethyl (R)-1-cyclopropyl-8-difluoromethoxy-7-[2-(2,2-dimethylpropanoyl)-1-methyl-2,3-dihydro-1H-5-isoindolyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylate, and the suspension is heated under reflux for 3 hours, after which 340 ml of water is added to the resulting mixture and 170 ml of the solvent is removed from the mixture by distillation under atmospheric pressure over 3 hours. The reaction mixture is cooled and thereafter 17 ml of ethanol is added to the mixture, after which the crystals deposited are collected by filtration. The resulting (R)-1-cyclopropyl-8-difluoromethoxy-7-(1-methyl-2,3-dihydro-1H-5-isoindolyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid hydrochloride is suspended in 340 ml of water and the pH of the mixture is adjusted to 7.5 with 2 moles/liter sodium hydroxide solution, after which the crystals deposited are collected by filtration to obtain 25.55 g of (R)-1-cyclopropyl-8-difluoromethoxy-7-(1-methyl-2,3-dihydro-1H-5-isoindolyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid monohydrate.

Workup

  1. temperaturethe suspension is heated
  2. temperatureunder reflux for 3 hours
  3. customis removed from the mixture by distillation under atmospheric pressure over 3 hours
  4. temperatureThe reaction mixture is cooled
  5. addition17 ml of ethanol is added to the mixture
  6. filtrationafter which the crystals deposited are collected by filtration
  7. filtrationafter which the crystals deposited are collected by filtration

Sources & evidence

ORD record
ord-90f76c2095c345118cf2f81edd337fc8
Source dataset
uspto-grants-2002_11
Patent number
US06482835B2

Reaction notes

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