Sodium hydride → Tert-butyl 4-[2-(4-methanesulfonyl-phenoxymethyl)pyridin-5-yl]piperidine-1-carboxylate

HRID 42136

Reaktionsgleichung

Reaktionsgleichung von HRID 42136
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[H-].[Na+].CS(O[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)=[CH:22][N:21]=1)(=O)=O.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([CH:26]3[CH2:27][CH2:28][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:30][CH2:31]3)=[CH:22][N:21]=2)=[CH:7][CH:6]=1)(=[O:3])=[O:4]

Komponenten

7

Edukt 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 1233504-(Methylsulfonyl)phenolHCID 86654264Tert-butyl 4-[2-(methanesulfonyloxymethyl)pyridin-5-yl]piperidine-1-carboxylate

Produkt 1

HCID 44819975Tert-butyl 4-[2-(4-methanesulfonyl-phenoxymethyl)pyridin-5-yl]piperidine-1-carboxylateAusbeute 12 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel3×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of 4-(methanesulfonyl)phenol (25 mg, 0.14 mmol) in dry tetrahydrofuran (0.5 mL) was added dropwise over 5 minutes to an ice-cooled suspension of sodium hydride (55% dispersion in mineral oil, 10 mg, 0.22 mmol) in dry tetrahydrofuran (0.5 mL). After stirring for an additional 20 minutes under N2, a solution of tert-butyl 4-[2-(methanesulfonyloxymethyl)pyridine-5-yl]piperidine-1-carboxylate (59 mg, 0.16 mmol) in dry tetrahydrofuran (0.5 mL) was added dropwise over 5 minutes to the mixture. The resulting mixture was stirred at room temperature for 2 hours and then refluxed overnight, to which was added saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2) to give a white solid. The solid was dissolved in ethyl acetate and extracted with 1N hydrochloric acid. The aqueous layer was neutralized by adding 1N sodium hydroxide and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound as a white crystal (7.5 mg, yield 11%).

Aufarbeitung

  1. temperaturecooled
  2. stirringThe resulting mixture was stirred at room temperature for 2 hours
  3. temperaturerefluxed overnight, to which
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2)
  9. customto give a white solid
  10. extractionextracted with 1N hydrochloric acid
  11. additionby adding 1N sodium hydroxide
  12. extractionextracted with ethyl acetate
  13. washThe organic layer was washed with brine
  14. dry with materialdried over anhydrous sodium sulfate
  15. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-d634bcbc85854868bacb7291224245b8
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536176B2

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