Water → HCID 20639576, compound

HRID 568271Notes

Reaction equation

HRID 568271 reaction equation
[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]

Participants

6

Reactant 3

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

Product 2

HCID 20639576HCID 20639576, compoundHCID 20639577HCID 20639577, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-f56c9dbf204644c4927d672b4cebfb71
Source dataset
uspto-grants-2001_01
Patent number
US06180622B2

Reaction notes

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