Sodium hydride → Ethyl 7-(1-t-butoxycarbonyl-3-pyrrolidinyloxy)-1-cyclopropyl-6-fluoro1,4-dihydro-4-oxoquinoline-3-carboxylate

HRID 465373Notes

Reaction equation

HRID 465373 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:15])=[C:11](F)[CH:12]=3)[C:7](=[O:16])[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:5]2)[CH2:3][CH2:2]1.[C:22]([O:26][C:27]([N:29]1[CH2:33][CH2:32][CH:31]([OH:34])[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C1CCN2C(=NCCC2)CC1.[H-].[Na+]>CN(C=O)C>[C:22]([O:26][C:27]([N:29]1[CH2:33][CH2:32][CH:31]([O:34][C:11]2[CH:12]=[C:13]3[C:8]([C:7](=[O:16])[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:5][N:4]3[CH:1]3[CH2:3][CH2:2]3)=[CH:9][C:10]=2[F:15])[CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 44169391-Boc-3-pyrrolidinolHCID 9817544Ethyl 1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate

Product 1

HCID 15021537Ethyl 7-(1-t-butoxycarbonyl-3-pyrrolidinyloxy)-1-cyclopropyl-6-fluoro1,4-dihydro-4-oxoquinoline-3-carboxylateYield 40.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 220 mg of ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate, 280 mg of 1-t-butoxycarbonyl-3-hydroxypyrrolidine, 170 mg of DBU and 5 ml of DMF was added 65 mg of 55% sodium hydride while the former was stirred at room temperature. The resultant mixture was stirred for 2 hours at room temperature and then at 45° C. for 11 hours. The reaction mixture was concentrated to dryness under reduced pressure. Chloroform was added to the residue to dissolve the latter. The resultant solution was washed successively with a 10% aqueous solution of citric acid, a 5% aqueous solution of sodium hydrogencarbonate and saturated saline. The resulting chloroform layer was dried over anhydrous sodium sulfate and then concentrated. The residue was purified by chromatography on silica gel (chloroform/methanol: 100/1), whereby 140 mg of ethyl 7-(1-t-butoxycarbonyl-3-pyrrolidinyloxy)-1-cyclopropyl-6-fluoro1,4-dihydro-4-oxoquinoline-3-carboxylate was obtained.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  2. additionChloroform was added to the residue
  3. dissolutionto dissolve the latter
  4. washThe resultant solution was washed successively with a 10% aqueous solution of citric acid
  5. dry with materialThe resulting chloroform layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel (chloroform/methanol: 100/1)

Sources & evidence

ORD record
ord-02fe183d948647db91f6032a18b3eb1b
Source dataset
uspto-grants-1992_10
Patent number
US05153203

Reaction notes

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