Sodium Iodide → 4-Nitrobenzyl (1r,5s,6s)-6-((1r)-1-hydroxyethyl)-2-[[(z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylate

HRID 2246102Notes

Reaction equation

HRID 2246102 reaction equation
[OH:1][CH2:2][C:3]1[N:4]=[CH:5][S:6][C:7]=1/[CH:8]=[CH:9]\[SH:10].C1(P(O[C:26]2[C@H:27]([CH3:50])[C@@H:28]3[C@@H:45]([C@H:46]([OH:48])[CH3:47])[C:44](=[O:49])[N:29]3[C:30]=2[C:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=2)=[O:32])(C2C=CC=CC=2)=O)C=CC=CC=1.[I-].[Na+].C(OCC)(=O)C>CC(C)=O.[Cl-].[Na+].O.[Ag]>[OH:48][C@@H:46]([C@H:45]1[C:44](=[O:49])[N:29]2[C:30]([C:31]([O:33][CH2:34][C:35]3[CH:36]=[CH:37][C:38]([N+:41]([O-:43])=[O:42])=[CH:39][CH:40]=3)=[O:32])=[C:26]([S:10]/[CH:9]=[CH:8]\[C:7]3[S:6][CH:5]=[N:4][C:3]=3[CH2:2][OH:1])[C@H:27]([CH3:50])[C@H:28]12)[CH3:47]

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 8857Ethyl AcetateHCID 15871605p-nitrobenzyl (1R,5R,6S)-2-(di-phenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylateHCID 875108504-Hydroxymethyl-5-[(z)-2-mercaptoethen-1-yl]thiazole

Product 1

HCID 694700964-Nitrobenzyl (1r,5s,6s)-6-((1r)-1-hydroxyethyl)-2-[[(z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylateYield 54.1%

Reagents, catalysts & solvents 3

HCID 23954SilverCatalystHCID 180AcetoneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

The crude crystal of the silver salt of 4-hydroxymethyl-5-[(Z)-2-mercaptoethen-1-yl]thiazole (283 mg) was added to 10 ml of a solution of 599 mg of 4-nitrobenzyl (1R,5R,6S)-2-(diphenylphosphoryloxy)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate in dry acetone under an argon atmosphere at 4° C., and 303 mg of sodium iodide was added thereto. The mixture was stirred at the same temperature for 18 hr. Ethyl acetate (20 ml) and 20 ml of semi-saturated brine were added thereto, and the mixture was filtered through Celite and was washed with ethyl acetate. The filtrate was separated, the organic layer was washed with semi-saturated brine, was dried over anhydrous magnesium sulfate, and was filtered, and ethyl acetate was removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (chloroform:methanol=20:1) to give 298 mg of 4-nitrobenzyl (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-2-[[(Z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylate.

Workup

  1. filtrationthe mixture was filtered through Celite
  2. washwas washed with ethyl acetate
  3. customThe filtrate was separated
  4. washthe organic layer was washed with semi-saturated brine
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. filtrationwas filtered
  7. customethyl acetate was removed by distillation under the reduced pressure
  8. customThe residue was purified by column chromatography on silica gel (chloroform:methanol=20:1)

Sources & evidence

ORD record
ord-97f5e3e31c8a48faac1da989481aa769
Source dataset
uspto-grants-2010_03
Patent number
US07687490B2

Reaction notes

Loading…