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

HRID 382613Notes

Reaction equation

HRID 382613 reaction equation
[OH:1][C@@H:2]([C@H:4]1[C:22](=[O:23])[N:6]2[C:7]([C:19]([OH:21])=O)=[C:8]([C:11]3[N:12]4[CH:18]=[N:17][CH:16]=[C:13]4[S:14][CH:15]=3)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].[C:24](=[O:27])([O-:26])O.[Na+].[CH3:29][OH:30]>O>[OH:1][C@@H:2]([C@H:4]1[C:22](=[O:23])[N:6]2[C:7]([C:19]([O:26][CH2:24][O:27][C:29](=[O:30])[C:4]([CH3:22])([CH3:5])[CH3:2])=[O:21])=[C:8]([C:11]3[N:12]4[CH:18]=[N:17][CH:16]=[C:13]4[S:14][CH:15]=3)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3]

Participants

5

Reactant 3

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 20698522(1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-3-yl)-1-methyl-1-carbapen-2-em-3-carboxylic Acid

Product 1

HCID 70299744Pivaloyloxymethyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-3-yl)-1-methyl-1-carbapen-2-em-3-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a suspension of 32.5 mg of (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-3-yl)-1-methyl-1-carbapen-2-em-3-carboxylic acid in a mixture of 10 ml of water and 8 ml of methanol was added 7.8 mg of sodium hydrogen carbonate, and the mixture was stirred at room temperature for 10 minutes to form a solution. Methanol was removed under reduced pressure, and the residue was lyophilized. The lyophilized product was dissolved in 2 ml of dry DMF, 0.03 ml of iodomethyl pivalate was added under the atmosphere of argon at −30° C., and the mixture was stirred for 2 hours during which the temperature was raised up to −10° C. Ethyl acetate was added to the reaction mixture, and the mixture was washed with semi-saturated aqueous saline. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to a total volume of 3 ml. The residue thus obtained was purified by column chromatography on silica gel (chloroform:methanol=30:1-10:1) to give 26.6 mg of the title compound.

Workup

  1. customto form a solution
  2. customMethanol was removed under reduced pressure
  3. dissolutionThe lyophilized product was dissolved in 2 ml of dry DMF
  4. addition0.03 ml of iodomethyl pivalate was added under the atmosphere of argon at −30° C.
  5. stirringthe mixture was stirred for 2 hours during which the temperature
  6. temperaturewas raised up to −10° C
  7. additionEthyl acetate was added to the reaction mixture
  8. washthe mixture was washed with semi-saturated aqueous saline
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure to a total volume of 3 ml
  12. customThe residue thus obtained
  13. customwas purified by column chromatography on silica gel (chloroform:methanol=30:1-10:1)

Sources & evidence

ORD record
ord-3dc853605e03474894e187492a930553
Source dataset
uspto-grants-2001_10
Patent number
US06310056B1

Reaction notes

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