Sodium Chloride → 8-((trans)-1-(Benzyloxycarbonyl)-3-fluoropiperidin-4-yloxy)quinoline 1-oxide

HRID 1095734Notes

Reaction equation

HRID 1095734 reaction equation
C([O:8]C(N1CC[C@@H](O[N+]2([O-])C3C(=CC=CC=3)C=CC2)[C@H](F)C1)=O)C1C=CC=CC=1.[F:30][C@H:31]1[C@H:36]([O:37][C:38]2[CH:39]=[CH:40][CH:41]=[C:42]3[C:47]=2[N:46]=[CH:45][CH:44]=[CH:43]3)[CH2:35][CH2:34][N:33]([C:48]([O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)=[O:49])[CH2:32]1.C1C=C(Cl)C=C(C(OO)=O)C=1.CC1C=C(Cl)C=CC=1OCCCC(O)=O.[O-]S([O-])(=S)=O.[Na+].[Na+].C([O-])(O)=O.[Na+].[Na+].[Cl-]>C(Cl)(Cl)Cl.CO>[CH2:51]([O:50][C:48]([N:33]1[CH2:34][CH2:35][C@@H:36]([O:37][C:38]2[CH:39]=[CH:40][CH:41]=[C:42]3[C:47]=2[N+:46]([O-:8])=[CH:45][CH:44]=[CH:43]3)[C@H:31]([F:30])[CH2:32]1)=[O:49])[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1

Participants

10

Reactant 7

HCID 5234Sodium ChlorideHCID 7207Butanoic acid, 4-(4-chloro-2-methylphenoxy)-HCID 24477Sodium ThiosulfateHCID 70297m-Chloroperbenzoic acid3×HCID 516892Sodium BicarbonateHCID 131729519(trans)-Benzyl 3-fluoro-4-(quinolin-8-yloxy)piperidine-1-carboxylateHCID 131729520(trans)-1-(Benzyloxycarbonyl-3-fluoropiperidin-4-yloxy)quinoline 1-oxide

Product 1

HCID 667821658-((trans)-1-(Benzyloxycarbonyl)-3-fluoropiperidin-4-yloxy)quinoline 1-oxideYield 96%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

Preparation of 8-((trans)-1-(benzyloxycarbonyl-3-fluoropiperidin-4-yloxy)quinoline 1-oxide: To a 0° C. solution of (trans)-benzyl 3-fluoro-4-(quinolin-8-yloxy)piperidine-1-carboxylate (1.0 g, 2.63 mmol) in 20 mL CHCl3 and 2 mL MeOH was added 77% max. mCPBA in 4×250 mg portions. The reaction mixture was stirred 20 minutes, then another 2×250 mg portions of 77% max. mCPBA was added (total 77% max. mCPBA (1.51 g, 6.57 mmol)). The reaction mixture was stirred 10 minutes, warmed to ambient temperature, and stirred another 3 hours, after which it was cooled to 0° C. Another 2 equivalents of 77% max. mCPB A was added in 4 equal portions, and the reaction mixture was warmed to ambient temperature and stirred an additional 1.5 hours. The reaction mixture was cooled to 0° C., and saturated Na2S2O3 was added, followed by saturated NaHCO3. The mixture was stirred 10 minutes, then warmed to ambient temperature and stirred another 30 minutes. Solid NaCl was added, and the mixture was extracted with CHCl3. The combined extracts were dried (Na2SO4), filtered, concentrated, and dried in vacuo to give 8-((trans)-1-(benzyloxycarbonyl)-3-fluoropiperidin-4-yloxy)quinoline 1-oxide (1.0 g, 2.52 mmol, 96.0% yield), which was used without further purification in the next step.

Workup

  1. stirringThe reaction mixture was stirred 10 minutes
  2. stirringstirred another 3 hours
  3. temperatureafter which it was cooled to 0° C
  4. temperaturethe reaction mixture was warmed to ambient temperature
  5. stirringstirred an additional 1.5 hours
  6. temperatureThe reaction mixture was cooled to 0° C.
  7. stirringThe mixture was stirred 10 minutes
  8. temperaturewarmed to ambient temperature
  9. stirringstirred another 30 minutes
  10. extractionthe mixture was extracted with CHCl3
  11. dry with materialThe combined extracts were dried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customdried in vacuo

Sources & evidence

ORD record
ord-e4a99fb0bd2f405faca1a038b20cd025
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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