Ammonium Chloride → allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidin-3-yl]thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylate

HRID 568231Notes

Reaction equation

HRID 568231 reaction equation
C[Mg]I.C(OCC)C.I[C:10]1[N:11]=[CH:12][N:13]2[CH:17]=[CH:16][S:15][C:14]=12.[CH2:18]([O:21][C:22]([N:24]1[C@H:28]([CH:29]=[O:30])[CH2:27][C@H:26]([S:31][C:32]2[C@H:33]([CH3:56])[C@@H:34]3[C@@H:44]([C@H:45]([O:47][Si:48]([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:50])[CH3:49])[CH3:46])[C:43](=[O:55])[N:35]3[C:36]=2[C:37]([O:39][CH2:40][CH:41]=[CH2:42])=[O:38])[CH2:25]1)=[O:23])[CH:19]=[CH2:20].[Cl-].[NH4+]>C1COCC1>[CH2:18]([O:21][C:22]([N:24]1[C@H:28]([CH:29]([OH:30])[C:10]2[N:11]=[CH:12][N:13]3[CH:17]=[CH:16][S:15][C:14]=23)[CH2:27][C@H:26]([S:31][C:32]2[C@H:33]([CH3:56])[C@@H:34]3[C@@H:44]([C@H:45]([O:47][Si:48]([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:49])[CH3:50])[CH3:46])[C:43](=[O:55])[N:35]3[C:36]=2[C:37]([O:39][CH2:40][CH:41]=[CH2:42])=[O:38])[CH2:25]1)=[O:23])[CH:19]=[CH2:20]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 177737777-Iodoimidazo[5,1-B]thiazoleHCID 131722311allyl(1R,5S,6S)-2-((3S,5S)-1-allyloxycarbonyl-5-formylpyrrolidin-3-yl)thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylateHCID 178467823HCID 178467823, compound

Product 1

HCID 131722318allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidin-3-yl]thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylateYield 40.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A 2 M methylmagnesium iodide/diethyl ether solution (1.30 ml) is diluted with 10 ml of anhydrous THF, and a solution of 650 mg of 7-iodoimidazo[5,1-b]thiazole in 10 ml of anhydrous THF is added dropwise to the diluted solution in an argon atmosphere over a period of 4 min. The mixture is stirred in this state at room temperature for additional 30 min. The internal temperature is lowered to −48° C., and the solution is added dropwise to a solution of 1.003 g of allyl(1R,5S,6S)-2-((3S,5S)-1-allyloxycarbonyl-5-formylpyrrolidin-3-yl)thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylate in 10 ml of anhydrous THF over a period of 5 min. The mixture is stirred in this state at −48 to −40° C. for 40 min, and the temperature is then raised to −25° C. over a period of 50 min. Semi-saturated aqueous ammonium chloride (50 ml) is added thereto, the mixture is extracted with 90 ml of ethyl acetate, and the organic layer is dried over anhydrous magnesium sulfate, followed by filtration and the removal of the solvent by evaporation to give a yellow viscous material. This viscous material is successively purified by column chromatography on Sephadex LH-20 (dichloromethane:methanol=1:1) and on silica gel (toluene:ethyl acetate=1:9) to give 491.3 mg of allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidin-3-yl]thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylate (a diastereomer mixture) as a yellow amorphous material.

Workup

  1. customis lowered to −48° C.
  2. stirringThe mixture is stirred in this state at −48 to −40° C. for 40 min
  3. temperaturethe temperature is then raised to −25° C. over a period of 50 min
  4. extractionthe mixture is extracted with 90 ml of ethyl acetate
  5. dry with materialthe organic layer is dried over anhydrous magnesium sulfate
  6. filtrationfollowed by filtration
  7. customthe removal of the solvent
  8. customby evaporation
  9. customto give a yellow viscous material
  10. customThis viscous material is successively purified by column chromatography on Sephadex

Sources & evidence

ORD record
ord-58ddcd8dd7954e2ba626a612499cc9a6
Source dataset
uspto-grants-2001_01
Patent number
US06180622B2

Reaction notes

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