N-Methylpiperidine → 2-tert-butoxycarbonylamino-N-[2-(4-chlorophenoxy)-1-methylethyl]-(2S)-butyramide

HRID 1900181

Reaktionsgleichung

Reaktionsgleichung von HRID 1900181
CN1CCCCC1.[C:8]([O:12][C:13]([NH:15][C@@H:16]([CH2:20][CH3:21])[C:17]([OH:19])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].ClC(OCC(C)C)=O.[Cl:30][C:31]1[CH:41]=[CH:40][C:34]([O:35][CH2:36][CH:37]([NH2:39])[CH3:38])=[CH:33][CH:32]=1>C(Cl)Cl.O>[C:8]([O:12][C:13]([NH:15][C@@H:16]([CH2:20][CH3:21])[C:17]([NH:39][CH:37]([CH3:38])[CH2:36][O:35][C:34]1[CH:40]=[CH:41][C:31]([Cl:30])=[CH:32][CH:33]=1)=[O:19])=[O:14])([CH3:9])([CH3:10])[CH3:11]

Komponenten

7

Edukt 4

HCID 12291N-MethylpiperidineHCID 62365Isobutyl chloroformateHCID 2755934(S)-2-((tert)-Butoxycarbonyl)amino)butanoic acidHCID 64846532-(4-Chloro-phenoxy)-1-methyl-ethylamine

Produkt 1

HCID 572516552-tert-butoxycarbonylamino-N-[2-(4-chlorophenoxy)-1-methylethyl]-(2S)-butyramideAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
-20 °C

Versuchsvorschrift

2.0 g of N-methylpiperidine was added to a solution containing 4.1 g of (2S)-2-tert-butoxycarbonylaminobutyric acid dissolved in 60 ml of methylene chloride, at -20° C. After the mixture was stirred for 10 minutes at the same temperature, 2.7 g of isobutyl chloroformate was added to the mixture at -40° C., and stirred for 1 hour at -20° C. 3.7 g of 2-(4-chlorophenoxy)-1-methylethylamine was added to this mixture at -60° C., and then the reaction mixture was allowed to sit and warm naturally to room temperature while being stirred, and was stirred for 20 hours at room temperature. Water was subsequently added to the reaction mixture. After the methylene chloride layer was washed successively with a 5% aqueous solution of sodium bicarbonate and water, the organic layer was dried over anhydrous magnesium sulfate and the methylene chloride was removed under reduced pressure. The obtained crude crystal was purified by column chromatography on silica gel, thus obtaining 5.6 g of the desired product in the form of a colorless glutinous substance (yield: 76%).

Aufarbeitung

  1. additionwas added to the mixture at -40° C.
  2. temperaturewarm naturally to room temperature
  3. stirringwhile being stirred
  4. stirringwas stirred for 20 hours at room temperature
  5. washAfter the methylene chloride layer was washed successively with a 5% aqueous solution of sodium bicarbonate and water
  6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  7. customthe methylene chloride was removed under reduced pressure
  8. customThe obtained crude crystal
  9. customwas purified by column chromatography on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-7a6234158c9d44f78f26e435a286684e
Quelldatensatz
uspto-grants-1996_11
Patentnummer
US05574064

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