Imidazole → HCID 11642579, compound

HRID 875056Notes

Reaction equation

HRID 875056 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][C:11]([F:18])=[C:12]([I:17])[CH:13]=2)[N:8]([C@H:19]([CH2:23][OH:24])[CH:20]([CH3:22])[CH3:21])[CH:7]=1)=[O:5])[CH3:2].N1C=CN=C1.[Si:30](Cl)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31].O>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][C:11]([F:18])=[C:12]([I:17])[CH:13]=2)[N:8]([C@H:19]([CH2:23][O:24][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH:20]([CH3:21])[CH3:22])[CH:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 58801740Ethyl 7-fluoro-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate

Product 1

HCID 11642579HCID 11642579, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound (150 g, 335 mmol) obtained in Step 3 was dissolved in dimethylformamide (500 ml), imidazole (30 g, 0.436 mmol) and tert-butyldimethylsilyl chloride (56 g, 369 mmol) were added, and the mixture was stirred at room temperature for 1.5 hr. Water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed successively with water, saturated aqueous ammonium chloride solution and saturated brine, and dried over sodium sulfate. The organic layer was filtered and the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (ethyl acetate:hexane=1:3 to 1:2) to give 1-((S)-1-tert-butyldimethylsilyloxymethyl-2-methylpropyl)-7-fluoro-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (173 g, yield 92%) as a colorless amorphous form.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed successively with water, saturated aqueous ammonium chloride solution and saturated brine
  3. dry with materialdried over sodium sulfate
  4. filtrationThe organic layer was filtered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe obtained residue was purified by silica gel chromatography (ethyl acetate:hexane=1:3 to 1:2)

Sources & evidence

ORD record
ord-c10a48d70f8043229f3a2edf1000c5d2
Source dataset
uspto-grants-2015_03
Patent number
US08981103B2

Reaction notes

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