Propargyl bromide → 1-Methoxy-4-{prop-2-ynyloxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester

HRID 1473772Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1473772
[CH3:1][O:2][C:3]([C:5]1([N:13]([OH:26])[C:14](=[O:25])[CH2:15][C:16]2[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][C:17]=2[CH3:24])[CH2:10][CH2:9][N:8]([O:11][CH3:12])[CH2:7][CH2:6]1)=[O:4].[H-].[Na+].[CH2:29](Br)[C:30]#[CH:31]>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1([N:13]([O:26][CH2:31][C:30]#[CH:29])[C:14](=[O:25])[CH2:15][C:16]2[C:17]([CH3:24])=[CH:18][C:19]([CH3:23])=[CH:20][C:21]=2[CH3:22])[CH2:6][CH2:7][N:8]([O:11][CH3:12])[CH2:9][CH2:10]1)=[O:4]

Komponenten

5

Edukt 3

HCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 584280024-{Hydroxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester

Produkt 1

HCID 584280801-Methoxy-4-{prop-2-ynyloxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 4-{hydroxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester (compound P3ii.3 obtained in analogy to preparation example 11, step 4) (500 mg, 1.37 mmol) in tetrahydrofuran (3 ml) at 0° C. was added sodium hydride (66 mg, 55% w/w dispersion in mineral oil, 1.51 mmol) in 2 portions. The reaction mixture was stirred at 0° C. for one hour, treated with propargyl bromide (202 mg, 1.65 mmol) dropwise, and further stirred at room temperature overnight. The reaction mixture was evaporated, diluted with ethyl acetate and filtered to remove salts. The filtrate was washed twice with brine, dried over sodium sulfate and concentrated. The oily residue was purified by chromatography on silica gel (ethyl acetate/hexane 1:2). Yield: 321 mg of 1-methoxy-4-{prop-2-ynyloxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester (compound P3ii.4) as a colorless gum.

Aufarbeitung

  1. stirringfurther stirred at room temperature overnight
  2. customThe reaction mixture was evaporated
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered
  5. customto remove salts
  6. washThe filtrate was washed twice with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe oily residue was purified by chromatography on silica gel (ethyl acetate/hexane 1:2)

Quellen und Nachweise

ORD-Eintrag
ord-09e42d57c8194d6cbda8295191c4c977
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09018135B2

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