Water → 6-(3-chloro-2-fluorobenzyl)-1-((S)-1-hydroxymethyl-2-methylpropyl)-7-methoxy-4-oxo-1,4-dihydroquinoline

HRID 391246Notes

Reaction equation

HRID 391246 reaction equation
C(OC(=O)[C:5]([C:14](=[O:33])[C:15]1[CH:20]=[C:19]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:23]=2[F:29])[C:18]([O:30][CH3:31])=[CH:17][C:16]=1F)=[CH:6][NH:7][C@H:8]([CH2:12][OH:13])[CH:9]([CH3:11])[CH3:10])C.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Cl:28][C:24]1[C:23]([F:29])=[C:22]([CH:27]=[CH:26][CH:25]=1)[CH2:21][C:19]1[CH:20]=[C:15]2[C:16](=[CH:17][C:18]=1[O:30][CH3:31])[N:7]([C@H:8]([CH2:12][OH:13])[CH:9]([CH3:10])[CH3:11])[CH:6]=[CH:5][C:14]2=[O:33]

Participants

5

Reactant 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 178472056HCID 178472056, compound

Product 1

HCID 866270746-(3-chloro-2-fluorobenzyl)-1-((S)-1-hydroxymethyl-2-methylpropyl)-7-methoxy-4-oxo-1,4-dihydroquinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 2-(5-(3-chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoyl)-3-((S)-1-hydroxymethyl-2-methylpropylamino)acrylic acid ethyl ester prepared in Step IX in N,N-dimethylformamide was added anhydrous potassium carbonate (4.86 g) with stirring at room temperature. After stirring at 95-105° C. for 6 hr, N,N-dimethylformamide (10 ml) and water (50 ml) were successively added dropwise at 65-75° C. to allow crystallization. After stirring for 1 hr, the mixture was cooled to room temperature, and further stirred for 1 hr. Water (20 ml) was further added and, after stirring for 1 hr, and the mixture was filtrated, and the residue was successively washed with 50% aqueous N,N-dimethylformamide solution (20 ml) and water (20 ml), and vacuum dried to give 6-(3-chloro-2-fluorobenzyl)-1-((S)-1-hydroxymethyl-2-methylpropyl)-7-methoxy-4-oxo-1,4-dihydroquinoline)-3-carboxylic acid ethyl ester (13.5 g).

Workup

  1. stirringAfter stirring at 95-105° C. for 6 hr
  2. customcrystallization
  3. stirringAfter stirring for 1 hr
  4. temperaturethe mixture was cooled to room temperature
  5. stirringfurther stirred for 1 hr
  6. additionWater (20 ml) was further added
  7. stirringafter stirring for 1 hr
  8. filtrationthe mixture was filtrated
  9. washthe residue was successively washed with 50% aqueous N,N-dimethylformamide solution (20 ml) and water (20 ml), and vacuum
  10. customdried

Sources & evidence

ORD record
ord-990599dfa7d143129b98bdab87bee858
Source dataset
uspto-grants-2013_02
Patent number
US08383819B2

Reaction notes

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