Hydrochloric Acid → (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[[(Z)-2-(4-(N-4-nitrobenzyloxycarbonyl-L-valyloxymethyl)thiazol-5-yl)ethen-1-yl]thio]-1-carbapen-2-em-3-carboxylic acid

HRID 1799735Notes

Reaction equation

HRID 1799735 reaction equation
[OH:1][C@@H:2]([C@H:4]1[C:47](=[O:48])[N:6]2[C:7]([C:41]([O:43]CC=C)=[O:42])=[C:8]([S:11]/[CH:12]=[CH:13]\[C:14]3[S:18][CH:17]=[N:16][C:15]=3[CH2:19][O:20][C:21](=[O:40])[C@H:22]([CH:37]([CH3:39])[CH3:38])[NH:23][C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][CH:29]=3)=[O:25])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].CC1(C)CC(=O)CC(=O)C1.C(OCC)(=O)C.Cl>O1CCCC1.[Cl-].[Na+].O>[OH:1][C@@H:2]([C@H:4]1[C:47](=[O:48])[N:6]2[C:7]([C:41]([OH:43])=[O:42])=[C:8]([S:11]/[CH:12]=[CH:13]\[C:14]3[S:18][CH:17]=[N:16][C:15]=3[CH2:19][O:20][C:21](=[O:40])[C@H:22]([CH:37]([CH3:39])[CH3:38])[NH:23][C:24]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][C:31]([N+:34]([O-:36])=[O:35])=[CH:32][CH:33]=3)=[O:25])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 31358DimedoneHCID 131728009Allyl (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[[(Z)-2-(4-(N-4-nitrobenzyloxycarbonyl-L-valinyloxy-methyl)thiazol-5-yl)ethen-1-yl]thio]-1-carbapen-2-em-3-carboxylate

Product 1

HCID 131728010(1R,5S,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[[(Z)-2-(4-(N-4-nitrobenzyloxycarbonyl-L-valyloxymethyl)thiazol-5-yl)ethen-1-yl]thio]-1-carbapen-2-em-3-carboxylic acidYield 67.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Allyl (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[[(Z)-2-(4-(N-4-nitrobenzyloxycarbonyl-L-valinyloxy-methyl)thiazol-5-yl)ethen-1-yl]thio]-1-carbapen-2-em-3-carboxylate (500 mg) and 250 mg of dimedone were dissolved in 10 ml of tetrahydrofuran. Tetrakistriphenylphosphine palladium (82 mg) was added to the solution, and the mixture was stirred under an argon atmosphere at room temperature for 30 min. The reaction mixture was poured into 50 ml of 20% brine and 50 ml of ethyl acetate, and the mixture was adjusted to pH 0.6 by the addition of a 1 N aqueous hydrochloric acid solution, followed by separation. The organic layer was dried over anhydrous magnesium sulfate, and the solid was removed by filtration, and the solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on Sephadex LH-20 (dichloromethane:methanol=1:1) to give 317 mg of (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[[(Z)-2-(4-(N-4-nitrobenzyloxycarbonyl-L-valyloxymethyl)thiazol-5-yl)ethen-1-yl]thio]-1-carbapen-2-em-3-carboxylic acid.

Workup

  1. customfollowed by separation
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. customthe solid was removed by filtration
  4. customthe solvent was removed by distillation under the reduced pressure
  5. customThe residue was purified by column chromatography on Sephadex

Sources & evidence

ORD record
ord-18fbf70288504569885dfb9920ba3010
Source dataset
uspto-grants-2013_01
Patent number
US08344154B2

Reaction notes

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