Ammonium Chloride → 1-Allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-5-yl)methyl]pyrrolidine

HRID 568268Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 568268
C([Mg]Br)C.C1COCC1.Br[C:11]1[N:18]2[C:14]([S:15][CH:16]=[CH:17]2)=[CH:13][N:12]=1.[CH2:19]([O:22][C:23]([N:25]1[C@H:29]([CH:30]=[O:31])[CH2:28][C@@H:27]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[CH2:26]1)=[O:24])[CH:20]=[CH2:21].[Cl-].[NH4+]>C1COCC1>[CH2:19]([O:22][C:23]([N:25]1[CH:29]([CH:30]([OH:31])[C:11]2[N:18]3[C:14]([S:15][CH:16]=[CH:17]3)=[CH:13][N:12]=2)[CH2:28][CH:27]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:34])[CH3:35])[CH2:26]1)=[O:24])[CH:20]=[CH2:21]

Komponenten

6

Edukt 4

HCID 25517Ammonium ChlorideHCID 183598575-Bromoimidazo[5,1-b]thiazoleHCID 22870383(2S,4R)-1-allyloxycarbonyl-4-t-butyldimethylsilyloxy-2-formylpyrrolidineHCID 178420660HCID 178420660, Verbindung

Produkt 1

HCID 212623911-Allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-5-yl)methyl]pyrrolidine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
-3 °C

Versuchsvorschrift

A 0.99 M ethylmagnesium bromide/THF solution (15.2 ml) is diluted with 60 ml of anhydrous THF. A solution of 3.046 g of 5-bromoimidazo[5,1-b]thiazole in 60 ml of anhydrous THF is added dropwise to the diluted solution in an argon atmosphere over a period of 15 min (4 to 8° C.), and the mixture is stirred in this state for 5 min. The mixture is then cooled to −3° C. over a period of 10 min. Thereafter, a solution of 4.702 g of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-formylpyrrolidine in 60 ml of anhydrous THF is added dropwise thereto over a period of 20 min (−3 to −1° C.). The mixture is stirred in this state at −1 to +1° C. for 80 min. An aqueous semi-saturated ammonium chloride solution (180 ml) is added thereto, and the mixture is extracted twice with 360 ml of ethyl acetate. The organic layer is dried over magnesium sulfate and filtered, and the solvent is removed by evaporation under reduced pressure to give a yellow oil which is then purified by flash column chromatography on silica gel (n-hexane:ethyl acetate=1:1 to 1:2) to give 4.934 g of 3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-5-yl)methyl]pyrrolidine (stereoisomer A, a high polar component) as a colorless amorphous material and 605.5 mg of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-5-yl)methyl]pyrrolidine(stereoisomer B, a low polar component) as a slightly yellow, high viscous material.

Aufarbeitung

  1. waitover a period of 20 min (−3 to −1° C.)
  2. stirringThe mixture is stirred in this state at −1 to +1° C. for 80 min
  3. extractionthe mixture is extracted twice with 360 ml of ethyl acetate
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent is removed by evaporation under reduced pressure
  7. customto give a yellow oil which
  8. customis then purified by flash column chromatography on silica gel (n-hexane:ethyl acetate=1:1 to 1:2)

Quellen und Nachweise

ORD-Eintrag
ord-e246e4f08e6040479504bd4c581dede7
Quelldatensatz
uspto-grants-2001_01
Patentnummer
US06180622B2

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