2-Bromoethanol → HCID 13054060, compound

HRID 223150Notes

Reaction equation

HRID 223150 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[N:21]=[C:20]3[C:15]([C:16](=[O:27])[C:17]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:18][NH:19]3)=[CH:14][C:13]=2[F:28])[CH2:8][CH2:7]1)=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:35](Br)[CH2:36][OH:37]>CN(C)C=O>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[N:21]=[C:20]3[C:15]([C:16](=[O:27])[C:17]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:18][N:19]3[CH2:35][CH2:36][OH:37])=[CH:14][C:13]=2[F:28])[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 108982-BromoethanolHCID 11430Potassium CarbonateHCID 12919356HCID 12919356, compound

Product 1

HCID 13054060HCID 13054060, compoundYield 87.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 7-(4-ethoxycarbonyl-1-piperazinyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate (10.5 g), dimethylformamide (100 ml), and potassium carbonate (7.4 g) was heated at 100° C. for 15 minutes. To the solution was added a solution of 10.1 g of ethylene bromohydrin in dimethylformamide (10 ml), and the mixture was heated at 100° C. for 45 minutes with stirring. After removal of the resulting inorganic substance by filtration, the filtrate was concentrated to dryness under reduced pressure. Water (80 ml) was added to the residue, and the resulting crystals were collected by filtration and recrystallized from ethanol to give 10.2 g of ethyl 7-(4-ethoxycarbonyl-1-piperazinyl)-6-fluoro-1-(2-hydroxyethyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate (mp 215°-217° C.). Thionyl chloride (5.0 g) was added to the solution of the resulting hydroxyethyl derivative (4.6 g) in chloroform (50 ml), and the mixture was refluxed under heating for 30 minutes. After cooling, the solution was treated with 30 ml of water and neutralized with a saturated sodium bicarbonate solution. The chloroform layer was separated, washed with water, and dried over anhydrous sodium sulfate. After removal of the solvent, the residue was chromatographed on silica gel with chloroform and the crystals resulting from the main fraction were recrystallized from ethyl acetate to give 4.7 g of ethyl 1-(2-chloroethyl)-7-(4-ethoxycarbonyl-1-piperazinyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate (mp 143°-144° C.).

Workup

  1. temperaturethe mixture was heated at 100° C. for 45 minutes
  2. customAfter removal of the resulting inorganic substance
  3. filtrationby filtration
  4. concentrationthe filtrate was concentrated to dryness under reduced pressure
  5. additionWater (80 ml) was added to the residue
  6. filtrationthe resulting crystals were collected by filtration
  7. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-c5dd158eb61e4d44ab2f652d2700718d
Source dataset
uspto-grants-1982_10
Patent number
US04352803

Reaction notes

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