Diethyl Ether → {1-[(5-Cyclopropyl-[1,3,4]oxadiazol-2-yl)-hydroxy-methyl]-propyl}-carbamic acid tert-butyl ester

HRID 1455589Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1455589
[CH:1]1([C:4]2[O:5][CH:6]=[N:7][N:8]=2)[CH2:3][CH2:2]1.[Li]CCCC.[Mg+2].[Br-].[Br-].O(CC)CC.[C:22]([O:26][C:27](=[O:34])[NH:28][CH:29]([CH:32]=[O:33])[CH2:30][CH3:31])([CH3:25])([CH3:24])[CH3:23]>C1COCC1>[C:22]([O:26][C:27](=[O:34])[NH:28][CH:29]([CH:32]([C:6]1[O:5][C:4]([CH:1]2[CH2:3][CH2:2]2)=[N:8][N:7]=1)[OH:33])[CH2:30][CH3:31])([CH3:23])([CH3:24])[CH3:25]

Komponenten

7

Edukt 5

HCID 3283Diethyl EtherHCID 82241Magnesium BromideHCID 11286906tert-butyl N-(1-oxobutan-2-yl)carbamateHCID 197768782-Cyclopropyl-1,3,4-oxadiazoleHCID 178418339Butyllithium

Produkt 1

HCID 68822601{1-[(5-Cyclopropyl-[1,3,4]oxadiazol-2-yl)-hydroxy-methyl]-propyl}-carbamic acid tert-butyl esterAusbeute 49 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

A solution of 2-cyclopropyl-[1,3,4]oxadiazole (2.16 g, 19.6 mmol) in dry THF (100 mL) is cooled to −78° C. nBuLi (1.6M in hexanes, 12.3 mL, 19.6 mmol) is added dropwise. The reaction mixture is stirred at −78° C. for 40 min. MgBr2.OEt2 (5.0692 g, 19.6 mmol) is added. The reaction mixture is allowed to warm up to −45° C. and stirred at that temperature for 1.5 hr. A solution of (1-formyl-propyl)-carbamic acid tert-butyl ester (3.7 g, 19.6 mmol) in THF (40 mL) is added. The reaction mixture is allowed to warm up to −20° C. and stirred at that temperature for 3.5 hrs. The reaction mixture is quenched with a solution of saturated NH4Cl solution and extracted with ethyl acetate. Combined organic extracts is washed with saturated NaCl solution and dried over MgSO4. The solvent is evaporated under reduced pressure and the crude is purified by column chromatography eluting with ethyl acetate and heptane mixture to give {1-[(5-cyclopropyl-[1,3,4]oxadiazol-2-yl)-hydroxy-methyl]-propyl}-carbamic acid tert-butyl ester (2.83 g, 49%).

Aufarbeitung

  1. additionis added dropwise
  2. temperatureto warm up to −45° C.
  3. stirringstirred at that temperature for 1.5 hr
  4. temperatureto warm up to −20° C.
  5. stirringstirred at that temperature for 3.5 hrs
  6. customThe reaction mixture is quenched with a solution of saturated NH4Cl solution
  7. extractionextracted with ethyl acetate
  8. washCombined organic extracts is washed with saturated NaCl solution
  9. dry with materialdried over MgSO4
  10. customThe solvent is evaporated under reduced pressure
  11. customthe crude is purified by column chromatography
  12. washeluting with ethyl acetate and heptane mixture

Quellen und Nachweise

ORD-Eintrag
ord-93a97c3767c244b9addf2079da96a648
Quelldatensatz
uspto-grants-2009_01
Patentnummer
US07482448B2

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