Water → pivaloyloxymethyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

HRID 382625Notes

Reaction equation

HRID 382625 reaction equation
[OH:1][C@@H:2]([C@H:4]1[C:21](=[O:22])[N:6]2[C:7]([C:18]([OH:20])=[O:19])=[C:8]([C:10]3[N:11]4[CH:17]=[N:16][CH:15]=[C:12]4[S:13][CH:14]=3)[CH2:9][C@H:5]12)[CH3:3].O.C(=O)([O-])O.[Na+].[C:29]([O:35][CH2:36]I)(=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31]>CN(C=O)C.C(OCC)(=O)C>[OH:1][C@@H:2]([C@H:4]1[C:21](=[O:22])[N:6]2[C:7]([C:18]([O:20][CH2:36][O:35][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])=[O:19])=[C:8]([C:10]3[N:11]4[CH:17]=[N:16][CH:15]=[C:12]4[S:13][CH:14]=3)[CH2:9][C@H:5]12)[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 104401Iodomethyl pivalateHCID 516892Sodium BicarbonateHCID 12070052(5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylic Acid

Product 1

HCID 12069985pivaloyloxymethyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 42.1 mg of (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylic acid 10 ml of water was added 1.3 ml of a 0.1 N aqueous sodium hydrogen carbonate solution, and the mixture was stirred at room temperature for 1 hour to form a solution, which was then lyophilized. The lyophilized product was dissolved in 1 ml of dry DMF, 0.034 ml of iodomethyl pivalate was added under the atmosphere of argon at −30° C., and the mixture was stirred for 1.5 hours during which the temperature was raised up to −10° C. The reaction mixture was diluted with 20 ml of ethyl acetate, and washed with semi-saturated aqueous saline. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to a volume of 3 ml, The residue thus obtained was purified by column chromatography on silica gel (chloroform:methanol=15:1) and on Sephadex LH-20 (chloroform:methanol=1:1) in this sequence to give 27.2 mg of the title compound.

Workup

  1. customto form a solution, which
  2. stirringthe mixture was stirred for 1.5 hours during which the temperature
  3. temperaturewas raised up to −10° C
  4. washwashed with semi-saturated aqueous saline
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure to a volume of 3 ml
  8. customThe residue thus obtained
  9. customwas purified by column chromatography on silica gel (chloroform:methanol=15:1) and on Sephadex

Sources & evidence

ORD record
ord-653d51819c7942ab9782cc38214fab45
Source dataset
uspto-grants-2001_10
Patent number
US06310056B1

Reaction notes

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