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

HRID 1461720Notes

Reaction equation

HRID 1461720 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 0.1M 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-efff3b121e6640bda6417591961f62c2
Source dataset
uspto-grants-1991_12
Patent number
US05077283

Reaction notes

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