Water → HCID 20639573, compound

HRID 568277Notes

Reaction equation

HRID 568277 reaction equation
C([Li])CCC.CCCCCC.[CH3:12][C:13]1[N:14]2[CH:20]=[N:19][CH:18]=[C:15]2[S:16][CH:17]=1.[CH2:21]([O:24][C:25]([N:27]1[C@H:31]([CH:32]=[O:33])[CH2:30][C@@H:29]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH2:28]1)=[O:26])[CH:22]=[CH2:23].O>C1COCC1>[CH2:21]([O:24][C:25]([N:27]1[C@H:31]([CH:32]([OH:33])[C:17]2[S:16][C:15]3=[CH:18][N:19]=[CH:20][N:14]3[C:13]=2[CH3:12])[CH2:30][C@@H:29]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:36])[CH3:37])[CH2:28]1)=[O:26])[CH:22]=[CH2:23]

Participants

6

Reactant 4

HCID 962WaterHCID 22631500HCID 22631500, compoundHCID 22870383(2S,4R)-1-allyloxycarbonyl-4-t-butyldimethylsilyloxy-2-formylpyrrolidineHCID 178418244HCID 178418244, compound

Product 1

HCID 20639573HCID 20639573, compoundYield 53.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 1.69 M n-butyllithium/n-hexane solution (7.4 ml) is added dropwise to a solution of 1.56 g of 3-methylimidazo[5,1-b]thiazole in 25 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 3.54 g of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-formylpyrrolidine in 15 ml of THF is gradually added dropwise to the mixed solution, the temperature is raised from −70° C. to 0° C. over a period of 3 hr, the mixture is stirred at 0° C. for 2 hr and at room temperature for 2 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 to give a crude product which is then successively purified by column chromatography on silica gel (ethyl acetate) and on Sephadex LH-20 (dichloromethane:methanol=1:1) to give 2.74 g of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(3-methylimidazo[5,1-b]thiazol-2-yl)methyl]pyrrolidine (a diastereomer mixture) as a colorless amorphous material.

Workup

  1. temperaturewhile maintaining the temperature at −70° C. or below
  2. temperaturethe temperature is raised from −70° C. to 0° C. over a period of 3 hr
  3. stirringthe mixture is stirred at 0° C. for 2 hr and at room temperature for 2 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. customto give a crude product which
  10. customis then successively purified by column chromatography on silica gel (ethyl acetate) and on Sephadex

Sources & evidence

ORD record
ord-e6b868b2180c46fdbecd5d43e380e860
Source dataset
uspto-grants-2001_01
Patent number
US06180622B2

Reaction notes

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