Potassium Iodide → 1-Cyclopropyl-7-[4-(diethoxyphosphinyl)-1-piperazinyl]-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid, 2-Methoxyethyl Ester

HRID 1196849

Reaction equation

HRID 1196849 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:28])=[C:11]([N:14]4[CH2:19][CH2:18][N:17]([P:20]([O:25][CH2:26][CH3:27])([O:22][CH2:23][CH3:24])=[O:21])[CH2:16][CH2:15]4)[CH:12]=3)[C:7](=[O:29])[C:6]([C:30]([OH:32])=[O:31])=[CH:5]2)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:39][O:40][CH2:41][CH2:42]Br.[OH-].[K+].[I-].[K+]>CN(C)P(N(C)C)(N(C)C)=O.CCOCC>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:28])=[C:11]([N:14]4[CH2:19][CH2:18][N:17]([P:20]([O:22][CH2:23][CH3:24])([O:25][CH2:26][CH3:27])=[O:21])[CH2:16][CH2:15]4)[CH:12]=3)[C:7](=[O:29])[C:6]([C:30]([O:32][CH2:42][CH2:41][O:40][CH3:39])=[O:31])=[CH:5]2)[CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 14797Potassium HydroxideHCID 809722-Bromoethyl methyl etherHCID 150280071-Cyclopropyl-7-[4-(diethoxyphosphinyl)-1-piperazinyl]-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid

Product 1

HCID 150280151-Cyclopropyl-7-[4-(diethoxyphosphinyl)-1-piperazinyl]-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid, 2-Methoxyethyl EsterYield 80.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

To a solution of 0.467 g of the product of Example 40 in 5 ml of hexamethylphosphoramide was added 0.163 g of cesium carbonate, 0.304 g of 2-bromoethyl methyl ether, 0.137 g of 45% aqueous potassium hydroxide and 0.017 g of potassium iodide. The suspension was stirred in the dark under argon for 8 days. Ether (40 ml) was added and the mixture was extracted successively with water, brine and water. The ether layer was discarded. The aqueous layers were extracted with chloroform, the chloroform extracts were dried over sodium sulfate and then evaporated, finally at <100° and 0.06 mm. to remove hexamethylphosphoramide. Two recrystallizations of the solid residue from methylene chloride-n-heptane gave 0.424 g of ivory-colored needles, m.p. 138°-141° C. The product was easily soluble in water and in 0.1 M phosphate buffer, pH 7.5.

Workup

  1. extractionthe mixture was extracted successively with water, brine and water
  2. extractionThe aqueous layers were extracted with chloroform
  3. dry with materialthe chloroform extracts were dried over sodium sulfate
  4. customevaporated, finally at <100°
  5. customto remove hexamethylphosphoramide
  6. customTwo recrystallizations of the solid residue from methylene chloride-n-heptane

Sources & evidence

ORD record
ord-a77687c3adb247d29ca7bb6d228e4a7b
Source dataset
uspto-grants-1992_05
Patent number
US05116827

Linked notes

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