Water → (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-2-yl)methyl]pyrrolidine

HRID 568271Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 568271
[S:1]1[CH:5]=[CH:4][N:3]2[CH:6]=[N:7][CH:8]=[C:2]12.[CH2:9]([O:12][C:13]([N:15]1[C@H:19]([CH:20]=[O:21])[CH2:18][C@@H:17]([O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[CH2:16]1)=[O:14])[CH:10]=[CH2:11].O>C1COCC1>[CH2:9]([O:12][C:13]([N:15]1[C@H:19]([CH:20]([OH:21])[C:5]2[S:1][C:2]3=[CH:8][N:7]=[CH:6][N:3]3[CH:4]=2)[CH2:18][C@@H:17]([O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:24])[CH3:25])[CH2:16]1)=[O:14])[CH:10]=[CH2:11].[CH2:9]([O:12][C:13]([N:15]1[C@H:19]([CH:20]([OH:21])[C:4]2[N:3]3[CH:6]=[N:7][CH:8]=[C:2]3[S:1][CH:5]=2)[CH2:18][C@@H:17]([O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:24])[CH3:25])[CH2:16]1)=[O:14])[CH:10]=[CH2:11]

Komponenten

6

Edukt 3

HCID 962WaterHCID 21262404Imidazo[5,1-b]thiazoleHCID 22870383(2S,4R)-1-allyloxycarbonyl-4-t-butyldimethylsilyloxy-2-formylpyrrolidine

Produkt 2

HCID 20639576(3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-2-yl)methyl]pyrrolidineHCID 20639577HCID 20639577, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A 1.69 M n-butyllithium-hexane solution (7.2 ml) is added dropwise to a solution of 2.09 g of imidazo[5,1-b]thiazole in 40 ml of dry THF over a period of 10 min while maintaining the temperature at −70° C. or below, and the mixture is stirred at that temperature for 2 hr. A solution of 5.32 g of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-formylpyrrolidine in 20 ml of THF is gradually added dropwise to the mixed solution, and the mixture is stirred at −70° C. for 1.5 hr. The temperature is raised to 0° C. over a period of one hr, and the mixture is stirred at 0° C. for one hr and further at room temperature for 1.5 hr. Water is added to the reaction solution, and the mixture is extracted three times with ethyl acetate. The organic layer is washed twice with saturated saline, dried over anhydrous magnesium sulfate, and filtered, and the solvent is removed by evaporation under reduced pressure. The resultant crude product is successively purified by column chromatography on Sephadex LH-20 (dichloromethane:methanol=1:1) and on silica gel (hexane:ethyl acetate=1:1) to give 0.92 g of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-2-yl)methyl]pyrrolidine (a diastereomer mixture) and 1.85 g of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-3-yl)methyl]pyrrolidine (a diastereomer mixture) as a yellow amorphous material.

Aufarbeitung

  1. temperaturewhile maintaining the temperature at −70° C. or below
  2. stirringthe mixture is stirred at −70° C. for 1.5 hr
  3. stirringthe mixture is stirred at 0° C. for one hr and further at room temperature for 1.5 hr
  4. extractionthe mixture is extracted three times with ethyl acetate
  5. washThe organic layer is washed twice with saturated saline
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customthe solvent is removed by evaporation under reduced pressure
  9. customThe resultant crude product is successively purified by column chromatography on Sephadex

Quellen und Nachweise

ORD-Eintrag
ord-f56c9dbf204644c4927d672b4cebfb71
Quelldatensatz
uspto-grants-2001_01
Patentnummer
US06180622B2

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