Sodium Hydroxide → 6-[(3-Chloro-2-fluorophenyl)methyl]-7-fluoro-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

HRID 875060Notes

Reaction equation

HRID 875060 reaction equation
C([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][C:11]([F:26])=[C:12]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=3[F:25])[CH:13]=2)[N:8]([C@H:27]([CH2:31][O:32][Si](C(C)(C)C)(C)C)[CH:28]([CH3:30])[CH3:29])[CH:7]=1)=[O:5])C.[OH-].[Na+]>C(O)(C)C>[Cl:24][C:20]1[C:19]([F:25])=[C:18]([CH:23]=[CH:22][CH:21]=1)[CH2:17][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[F:26])[N:8]([C@H:27]([CH2:31][OH:32])[CH:28]([CH3:30])[CH3:29])[CH:7]=[C:6]([C:4]([OH:5])=[O:3])[C:15]2=[O:16]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 11685643HCID 11685643, compound

Product 1

HCID 588017116-[(3-Chloro-2-fluorophenyl)methyl]-7-fluoro-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acidYield 83.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

1-((S)-1-tert-butyldimethylsilyloxymethyl-2-methylpropyl)-6-(3-chloro-2-fluorobenzyl)-7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (19 g, 33 mmol) obtained in Example 1, Step 5 was dissolved in isopropanol (100 ml), 1N aqueous sodium hydroxide solution (200 ml, 200 mmol) was added, and the mixture was heated under reflux for 2.5 hr. The reaction mixture was allowed to cool to room temperature, and the mixture was filtered through Celite. The filtrate was acidified by adding concentrated hydrochloric acid, and stirred room temperature for 2 hr. The precipitated solid was collected by filtration and vacuum dried to give 6-(3-chloro-2-fluorobenzyl)-7-fluoro-1-((S)-1-hydroxymethyl-2-methylpropyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (12 g, yield 82%) as a pale-yellow solid.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2.5 hr
  3. filtrationthe mixture was filtered through Celite
  4. additionby adding concentrated hydrochloric acid
  5. filtrationThe precipitated solid was collected by filtration and vacuum
  6. customdried

Sources & evidence

ORD record
ord-86f9c637e469493c9262945dabf3235e
Source dataset
uspto-grants-2015_03
Patent number
US08981103B2

Reaction notes

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