Sodium hydride → HCID 15021538, compound

HRID 465375Notes

Reaction equation

HRID 465375 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11](F)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.[C:23]([O:27][C:28]([N:30]1[CH2:34][CH2:33][CH:32]([OH:35])[CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C1CCN2C(=NCCC2)CC1.[H-].[Na+]>CN(C=O)C>[C:23]([O:27][C:28]([N:30]1[CH2:34][CH2:33][CH:32]([O:35][C:11]2[C:12]([F:14])=[C:13]3[C:8]([C:7](=[O:17])[C:6]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:5][N:4]3[CH:1]3[CH2:2][CH2:3]3)=[CH:9][C:10]=2[F:16])[CH2:31]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 5354151-Cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid Ethyl EsterHCID 44169391-Boc-3-pyrrolidinol

Product 1

HCID 15021538HCID 15021538, compoundYield 58.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 233 mg of ethyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate, 168 mg of 1-t-butoxycarbonyl-3-hydroxypyrrolidine, 170 mg of DBU and 5 xl of DMF was added 36 mg of 55% sodium hydride while the former was stirred at room temperature. After the resultant mixture was stirred for 1 hour at room temperature, the reaction mixture was concentrated to dryness under reduced pressure. After chloroform and 10% citric acid were added to the residue and the resultant mixture was shaken thoroughly, the resulting chloroform layer was collected and then successively washed with a 5% aqueous solution of sodium hydrogencarbonate and saturated saline. The chloroform solution was dried over anhydrous sodium sulfate and then concentrated. The residue was purified by chromatography on silica gel (chloroform/methanol: 100:1), whereby 210 mg of ethyl 7-(1-t-butoxycarbonyl-3-pyrrolidinyloxy)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate was obtained.

Workup

  1. concentrationthe reaction mixture was concentrated to dryness under reduced pressure
  2. additionAfter chloroform and 10% citric acid were added to the residue
  3. stirringthe resultant mixture was shaken thoroughly
  4. customthe resulting chloroform layer was collected
  5. washsuccessively washed with a 5% aqueous solution of sodium hydrogencarbonate and saturated saline
  6. dry with materialThe chloroform solution was dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on silica gel (chloroform/methanol: 100:1)

Sources & evidence

ORD record
ord-924f6b530c634bd3a526df38747d78fe
Source dataset
uspto-grants-1992_10
Patent number
US05153203

Reaction notes

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