Benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylate → Benzyl 3-(diethoxyphosphorylamino)-4-methylpiperidine-1-carboxylate

HRID 73559Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 73559
[CH3:1][Mg]Br.[CH2:4]([O:6][P:7]([N:12]1[CH:18]2[CH:13]1[CH2:14][CH2:15][N:16]([C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20])[CH2:17]2)([O:9][CH2:10][CH3:11])=[O:8])[CH3:5]>C1COCC1.[Cu]I>[CH2:4]([O:6][P:7]([NH:12][CH:18]1[CH:13]([CH3:1])[CH2:14][CH2:15][N:16]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:17]1)([O:9][CH2:10][CH3:11])=[O:8])[CH3:5]

Komponenten

5

Edukt 2

HCID 59455678Benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylateHCID 178418573HCID 178418573, Verbindung

Produkt 1

HCID 60205257Benzyl 3-(diethoxyphosphorylamino)-4-methylpiperidine-1-carboxylateAusbeute 35 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
10 °C

Versuchsvorschrift

To a suspension of CuI (0.3 equiv.) in anhydrous THF (0.1M) was added methyl magnesium bromide (3M solution in Et2O, 10 equiv.) at −40° C. The reaction was stirred for 30 min, followed by addition of benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylate (1.0 equiv.) in THF (0.1M) at −40° C. Allowed the reaction to warm to 10° C. over 5 h, then quenched with water and extracted with ethyl acetate. The organic phase was concentrated under vacuo and purified via silica gel column chromatography eluting with ethyl acetate and hexanes (50% to 100% ethyl acetate) to yield benzyl 3-(diethoxyphosphorylamino)-4-methylpiperidine-1-carboxylate in 35% yield. LCMS (m/z): 385.0 (MH+), Rt=3.38 min.

Aufarbeitung

  1. customAllowed the reaction
  2. customquenched with water
  3. extractionextracted with ethyl acetate
  4. concentrationThe organic phase was concentrated under vacuo
  5. custompurified via silica gel column chromatography
  6. washeluting with ethyl acetate and hexanes (50% to 100% ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-0db8e0a420254cecb1c79e6ff76e14c6
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08829193B2

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