Imidazole → (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-(5-chloroimidazo[5,1-b]thiazol-2-yl)-1-(methylthiothiocarbonyloxy)methyl]pyrrolidine

HRID 568294Notes

Reaction equation

HRID 568294 reaction equation
[CH2:1]([O:4][C:5]([N:7]1[C@H:11]([CH:12]([C:14]2[S:18][C:17]3=[CH:19][N:20]=[C:21]([Cl:22])[N:16]3[CH:15]=2)[OH:13])[CH2:10][C@@H:9]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:8]1)=[O:6])[CH:2]=[CH2:3].N1C=CN=C1.[H-].[Na+].[CH3:38]I.[C:40](=[S:42])=[S:41]>C1COCC1.C(OCC)(=O)C>[CH2:1]([O:4][C:5]([N:7]1[C@H:11]([CH:12]([C:14]2[S:18][C:17]3=[CH:19][N:20]=[C:21]([Cl:22])[N:16]3[CH:15]=2)[O:13][C:40]([S:42][CH3:38])=[S:41])[CH2:10][C@@H:9]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:25])[CH3:26])[CH2:8]1)=[O:6])[CH:2]=[CH2:3]

Participants

8

Reactant 5

HCID 795ImidazoleHCID 6328Methyl iodideHCID 6348Carbon DisulfideHCID 24758Sodium hydrideHCID 70217392(3R,5S)-1-Allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-(5-chloroimidazo[5,1-b]thiazol-2-yl)-1-hydroxymethyl]pyrrolidine

Product 1

HCID 20639569(3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-(5-chloroimidazo[5,1-b]thiazol-2-yl)-1-(methylthiothiocarbonyloxy)methyl]pyrrolidine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3R,5S)-1-Allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-(5-chloroimidazo[5,1-b]thiazol-2-yl)-1-hydroxymethyl]pyrrolidine (a diastereomer mixture) (2.300 g) and 3.3 mg of imidazole are dissolved in 24.5 ml of anhydrous THF. Carbon disulfide (0.44 ml) and 292 mg of 60% sodium hydride are successively added to the solution in an argon atmosphere on ice bath, and the mixture is stirred in this state for 20 min. Methyl iodide (0.32 ml) is added dropwise thereto, and the mixture is stirred in this state for one hr. The reaction solution is diluted with 250 ml of ethyl acetate, washed with semi-saturated saline, and dried over anhydrous magnesium sulfate. The solvent is removed by evaporation under reduced pressure to give a crude product which is then purified by column chromatography on silica gel (hexane:ethyl acetate=3:1) to give 2.607 g of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-(5-chloroimidazo[5,1-b]thiazol-2-yl)-1-(methylthiothiocarbonyloxy)methyl]pyrrolidine (a diastereomer mixture) as a yellow viscous material.

Workup

  1. stirringthe mixture is stirred in this state for one hr
  2. washwashed with semi-saturated saline
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent is removed by evaporation under reduced pressure
  5. customto give a crude product which
  6. customis then purified by column chromatography on silica gel (hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-8530f4f88d12432880b06d5f39ab2673
Source dataset
uspto-grants-2001_01
Patent number
US06180622B2

Reaction notes

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