Acetic Acid → HCID 131722297, compound

HRID 568218Notes

Reaction equation

HRID 568218 reaction equation
C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.[CH2:28]([O:31][C:32]([N:34]1[C@H:38]([C:39]([N:41]([CH2:43][C:44]2[N:45]3[C:51]([CH2:52][NH:53][C:54]([O:56][CH2:57][CH:58]=[CH2:59])=[O:55])=[N:50][CH:49]=[C:46]3[S:47][CH:48]=2)[CH3:42])=[O:40])[CH2:37][C@H:36]([S:60][C:61]2[C@H:62]([CH3:85])[C@@H:63]3[C@@H:73]([C@H:74]([O:76][Si](C(C)(C)C)(C)C)[CH3:75])[C:72](=[O:84])[N:64]3[C:65]=2[C:66]([O:68][CH2:69][CH:70]=[CH2:71])=[O:67])[CH2:35]1)=[O:33])[CH:29]=[CH2:30].P([O-])([O-])([O-])=O>C1COCC1>[CH2:28]([O:31][C:32]([N:34]1[C@H:38]([C:39]([N:41]([CH2:43][C:44]2[N:45]3[C:51]([CH2:52][NH:53][C:54]([O:56][CH2:57][CH:58]=[CH2:59])=[O:55])=[N:50][CH:49]=[C:46]3[S:47][CH:48]=2)[CH3:42])=[O:40])[CH2:37][C@H:36]([S:60][C:61]2[C@H:62]([CH3:85])[C@@H:63]3[C@@H:73]([C@H:74]([OH:76])[CH3:75])[C:72](=[O:84])[N:64]3[C:65]=2[C:66]([O:68][CH2:69][CH:70]=[CH2:71])=[O:67])[CH2:35]1)=[O:33])[CH:29]=[CH2:30]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1061PhosphateHCID 11078149TBAF tetrahydrofuranHCID 131722298HCID 131722298, compound

Product 1

HCID 131722297HCID 131722297, compoundYield 81.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Acetic acid (0.30 ml) and 1.75 ml of a 1 M tetra-n-butylammonium fluoride/THF solution are added to a solution of 300 mg of allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[N-[5-(allyloxycarbonylaminomethyl)imidazo[5,1-b]thiazol-3-yl]methyl-N-methylaminocarbonyl]pyrrolidin-3-yl]thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylate in 5.2 ml of anhydrous THF, and the mixture is stirred in an argon atmosphere at room temperature for 27.5 hr. 1/15 M phosphate buffer (pH 7.0) (10 ml) is added thereto, and the mixture is extracted twice with 30 ml of ethyl acetate. The combined organic layers are dried over a 1:1 mixture of anhydrous magnesium sulfate and potassium carbonate and filtered, and the solvent is removed under reduced pressure and by filtrate to give a colorless viscous material. The viscous material is successively purified by column chromatography on silica gel (ethyl acetate:methanol=97:3 to 95:5) and on Sephadex LH-20 (chloroform:methanol=1:1) to give 212.6 mg of allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[N-[5-(allyloxycarbonylaminomethyl)imidazo[5,1-b]thiazol-3-yl]methyl-N-methylaminocarbonyl]pyrrolidin-3-yl]thio-6-((1R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate as a colorless amorphous material.

Workup

  1. extractionthe mixture is extracted twice with 30 ml of ethyl acetate
  2. dry with materialThe combined organic layers are dried over a 1:1 mixture of anhydrous magnesium sulfate and potassium carbonate
  3. filtrationfiltered
  4. customthe solvent is removed under reduced pressure and by filtrate
  5. customto give a colorless viscous material
  6. customThe viscous material is successively purified by column chromatography on silica gel (ethyl acetate:methanol=97:3 to 95:5) and on Sephadex

Sources & evidence

ORD record
ord-247bc9967db04e0cbfa38c3296a32641
Source dataset
uspto-grants-2001_01
Patent number
US06180622B2

Reaction notes

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