Ethyl Acetate → 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

HRID 1799734Notes

Reaction equation

HRID 1799734 reaction equation
[OH:1][C@@H:2]([C@H:4]1[C:27](=[O:28])[N:6]2[C:7]([C:21]([O:23][CH2:24][CH:25]=[CH2:26])=[O:22])=[C:8]([S:11]/[CH:12]=[CH:13]\[C:14]3[S:18][CH:17]=[N:16][C:15]=3[CH2:19][OH:20])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].Cl.CN(C)CCCN=C=NCC.[N+:41]([C:44]1[CH:61]=[CH:60][C:47]([CH2:48][O:49][C:50]([NH:52][C@H:53]([C:57](O)=[O:58])[CH:54]([CH3:56])[CH3:55])=[O:51])=[CH:46][CH:45]=1)([O-:43])=[O:42].C(OCC)(=O)C>CN(C)C(=O)C.CN(C)C1C=CN=CC=1.[Cl-].[Na+].O>[OH:1][C@@H:2]([C@H:4]1[C:27](=[O:28])[N:6]2[C:7]([C:21]([O:23][CH2:24][CH:25]=[CH2:26])=[O:22])=[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:57](=[O:58])[C@H:53]([CH:54]([CH3:55])[CH3:56])[NH:52][C:50]([O:49][CH2:48][C:47]3[CH:60]=[CH:61][C:44]([N+:41]([O-:43])=[O:42])=[CH:45][CH:46]=3)=[O:51])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 54494215L-Valine, N-[[(4-nitrophenyl)methoxy]carbonyl]-HCID 69471839Allyl (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

Product 1

HCID 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-carboxylateYield 32.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 31374DimethylacetamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Allyl (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 (970 mg) was dissolved in 10 ml of N,N-dimethylacetamide. 4-Dimethylaminopyridine (281 mg), 441 mg of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride, and 681 mg of N-4-nitrobenzyloxycarbonyl-L-valine were added to the solution, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into 50 ml of 20% brine and 50 ml of ethyl acetate, followed by separation. The organic layer was dried over magnesium sulfate. The magnesium sulfate was removed by filtration, and the solvent was removed by distillation under the reduced pressure. The crude product was purified by column chromatography on silica gel (ethyl acetate:n-hexane=2:1, and subsequently ethyl acetate:n-hexane=5:1) to give 517 mg of allyl (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-carboxylate.

Workup

  1. customfollowed by separation
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. customThe magnesium sulfate was removed by filtration
  4. customthe solvent was removed by distillation under the reduced pressure
  5. customThe crude product was purified by column chromatography on silica gel (ethyl acetate

Sources & evidence

ORD record
ord-1c640564d51248afb91aaa3279a4f1e9
Source dataset
uspto-grants-2013_01
Patent number
US08344154B2

Reaction notes

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