Triethylamine → 364069-14-7

HRID 2183686Notes

Reaction equation

HRID 2183686 reaction equation
Cl.Cl.[NH2:3][C@H:4]1[C:8]2([CH2:10][CH2:9]2)[CH2:7][NH:6][CH2:5]1.C(N(CC)CC)C.F[B]F.[F:21][C:22]1[CH:23]=[C:24]2[C:29](=[C:30]([O:33][CH3:34])[C:31]=1F)[N:28]([C@@H:35]1[CH2:37][C@@H:36]1[F:38])[CH:27]=[C:26]([C:39]([OH:41])=[O:40])[C:25]2=[O:42]>CS(C)=O>[NH2:3][C@H:4]1[C:8]2([CH2:10][CH2:9]2)[CH2:7][N:6]([C:31]2[C:30]([O:33][CH3:34])=[C:29]3[C:24]([C:25](=[O:42])[C:26]([C:39]([OH:41])=[O:40])=[CH:27][N:28]3[C@@H:35]3[CH2:37][C@@H:36]3[F:38])=[CH:23][C:22]=2[F:21])[CH2:5]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 23539486(7S)-5-Azaspiro[2.4]heptan-7-amine--hydrogen chloride (1/2)HCID 86589737HCID 86589737, compound

Product 1

HCID 5271826364069-14-7Yield 61.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

(7S)-7-Amino-5-azaspiro[2.4]heptane dihydrochloride (61.4 g; 0.332 mol) was dissolved in dimethylsulfoxide (800 ml), and triethylamine (138 ml; 0.994 mol) was added to the resultant solution under a nitrogen atmosphere at room temperature, followed by stirring for 10 hours. 6,7-Difluoro-1-[(1R, 2S)-2-fluoro-1-cyclopropyl]-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid difluoroboron chelate (100 g; 0.276 mol) in powder form was slowly added to the reaction mixture, followed by stirring for 40 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and ethanol (90%: 1000 ml) and triethylamine (20 ml) were added thereto, followed by refluxing for 2.5 hours. The reaction mixture was left to cool, and crystals that precipitated were collected by filtration. The crystals were sequentially washed with ethanol and ether, followed by drying under reduced pressure at 70° C. for 16 hours, to thereby yield 72.5 g of the title compound (as 0.5 hydrate) as a pale yellow powder (yield: 61.4%). Solvents were removed from the filtrate under reduced pressure, and water (2000 ml) was added to the residue. An aqueous sodium hydroxide solution (3N) was added to the mixture so as to adjust the pH value to 10.0 while being stirred under ice cooling. Subsequently, an aqueous hydrochloric acid solution (3N) was added to the mixture so as to adjust the pH to 7.4, followed by stirring for 16 hours at room temperature. Crystals that precipitated were collected by filtration, washed with water, and dried under reduced pressure at 70° C., to thereby yield 19.2 g of the title compound (as 0.5 hydrate) as a pale yellow powder (yield: 33.6%).

Workup

  1. stirringby stirring for 40 hours at room temperature
  2. concentrationThe reaction mixture was concentrated under reduced pressure, and ethanol (90%: 1000 ml) and triethylamine (20 ml)
  3. additionwere added
  4. temperatureby refluxing for 2.5 hours
  5. waitThe reaction mixture was left
  6. temperatureto cool
  7. customcrystals that precipitated
  8. filtrationwere collected by filtration
  9. washThe crystals were sequentially washed with ethanol and ether
  10. customby drying under reduced pressure at 70° C. for 16 hours

Sources & evidence

ORD record
ord-5ffdd14dbbef471aa990d1908169855e
Source dataset
uspto-grants-2005_05
Patent number
US06900225B2

Reaction notes

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