Ethanol → Diisopropyl Ether

HRID 1415943Notes

Reaction equation

HRID 1415943 reaction equation
C([NH:8][C@H:9]([C:13]([OH:15])=O)[CH:10]([CH3:12])[CH3:11])(O[C:4](C)([CH3:6])[CH3:5])=O.[CH3:16]N1CCOCC1.ClC(OCC(C)C)=O.[NH2:31][C@H:32]1[CH2:36][CH2:35][N:34]([C:37]2[N:46]=[C:45]3[C:40]([C:41](=[O:63])[C:42]([C:58]([O:60]CC)=[O:59])=[CH:43][N:44]3[C:47]3[CH:52]=[C:51]([NH:53]C=O)[C:50]([F:56])=[CH:49][C:48]=3[F:57])=[CH:39][C:38]=2[F:64])[CH2:33]1.[CH2:65]([OH:67])[CH3:66]>ClCCl.O.C(Cl)(Cl)Cl>[CH:65]([O:67][CH:4]([CH3:6])[CH3:5])([CH3:16])[CH3:66].[NH2:53][C:51]1[CH:52]=[C:47]([N:44]2[C:45]3[C:40](=[CH:39][C:38]([F:64])=[C:37]([N:34]4[CH2:35][CH2:36][C@H:32]([NH:31][C:13](=[O:15])[C@H:9]([CH:10]([CH3:11])[CH3:12])[NH2:8])[CH2:33]4)[N:46]=3)[C:41](=[O:63])[C:42]([C:58]([OH:60])=[O:59])=[CH:43]2)[C:48]([F:57])=[CH:49][C:50]=1[F:56]

Participants

10

Reactant 5

HCID 702EthanolHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 83693Boc-L-ValineHCID 86754100HCID 86754100, compound

Product 2

HCID 7914Diisopropyl EtherHCID 69959176HCID 69959176, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-20 °C

Procedure

To 5 ml of dichloromethane were added 220 mg of N-Boc-L-valine and 106 mg of N-methylmorpholine. With stirring at -20° C., 140 μl of isobutyl chloroformate was added to the solution, which was stirred for 20 minutes. This solution was cooled to -60° C., and a dispersion of 475 mg of ethyl 7-[(3S)-3-aminopyrrolidin-1-yl]-1-(2,4-difluoro-5-formylaminophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate in 10 ml of dichloromethane was added thereto. The solution was allowed to slowly warm up to room temperature and then stirred at 40° C. for 30 minutes. To the solution was added 20 ml of chloroform and 10 ml of distilled water. The solution was separated, dried over anhydrous magnesium sulfate, and concentrated in vacua. A half fraction of the bubbly solidified residue was dissolved in a mixture of 3 ml of 1N hydrochloric acid and 3 ml of ethanol, and the solution was stirred at 100° C. for 1.5 hours. The solution was concentrated in vacua, 3 ml of 1N hydrochloric acid was added to the residue, and the solution was stirred at 100° C. for 40 minutes. The solution was concentrated in vacua and the residue was dissolved in 2 ml of distilled water. The solution was neutralized to about pH 8 by adding a 10% sodium hydroxide aqueous solution little by little, causing a precipitate to form. With 2 ml of ethanol added, the solution was heated at reflux for 30 minutes and allowed to stand. The precipitate was collected by filtration, and washed with ethanol and then diisopropyl ether to give 141 mg of the title compound.

Workup

  1. stirringwas stirred for 20 minutes
  2. temperatureThis solution was cooled to -60° C.
  3. temperatureto slowly warm up to room temperature
  4. stirringstirred at 40° C. for 30 minutes
  5. customThe solution was separated
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacua
  8. dissolutionA half fraction of the bubbly solidified residue was dissolved in a mixture of 3 ml of 1N hydrochloric acid and 3 ml of ethanol
  9. stirringthe solution was stirred at 100° C. for 1.5 hours
  10. concentrationThe solution was concentrated in vacua, 3 ml of 1N hydrochloric acid
  11. additionwas added to the residue
  12. stirringthe solution was stirred at 100° C. for 40 minutes
  13. concentrationThe solution was concentrated in vacua
  14. dissolutionthe residue was dissolved in 2 ml of distilled water
  15. additionby adding a 10% sodium hydroxide aqueous solution little by little,
  16. customto form
  17. temperaturethe solution was heated
  18. temperatureat reflux for 30 minutes
  19. filtrationThe precipitate was collected by filtration
  20. washwashed with ethanol

Sources & evidence

ORD record
ord-8583e0b83c154410a215d47510cb925e
Source dataset
uspto-grants-1999_06
Patent number
US05910498

Reaction notes

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