Diisopropylethylamine → HCID 131725315, compound

HRID 891500Notes

Reaction equation

HRID 891500 reaction equation
C([S:4][CH:5]1[CH2:8][N:7]([C:9]2[S:10][CH:11]=[C:12]([C:14](=[O:28])[NH:15][C@H:16]([CH2:19][O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[CH2:17][CH3:18])[N:13]=2)[CH2:6]1)(=O)C.C(O)(=O)C.NN.C1(P(O[C:50]2[C@H:51]([CH3:74])[C@H:52]3[C@@H:69]([C@H:70]([OH:72])[CH3:71])[C:68](=[O:73])[N:53]3[C:54]=2[C:55]([O:57][CH2:58][C:59]2[CH:64]=[CH:63][C:62]([N+:65]([O-:67])=[O:66])=[CH:61][CH:60]=2)=[O:56])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.C(#N)C.C(OCC)(=O)C>[Si:21]([O:20][CH2:19][C@@H:16]([NH:15][C:14]([C:12]1[N:13]=[C:9]([N:7]2[CH2:8][CH:5]([S:4][C:50]3[C@H:51]([CH3:74])[C@@H:52]4[C@@H:69]([C@H:70]([OH:72])[CH3:71])[C:68](=[O:73])[N:53]4[C:54]=3[C:55]([O:57][CH2:58][C:59]3[CH:64]=[CH:63][C:62]([N+:65]([O-:67])=[O:66])=[CH:61][CH:60]=3)=[O:56])[CH2:6]2)[S:10][CH:11]=1)=[O:28])[CH2:17][CH3:18])([C:24]([CH3:25])([CH3:26])[CH3:27])([CH3:23])[CH3:22]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 165591Hydrazine, acetate (1:1)HCID 516892Sodium BicarbonateHCID 58595136HCID 58595136, compoundHCID 131720384p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131725315HCID 131725315, compoundYield 90.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-acetylthio-1-{4-[(1S)-1-(t-butyidimethylsilyloxymethyl)-propylcarbamoyl]-1,3-thiazol-2-yl}azetidine (610 mg, 1.37 mmol) (obtained as described in Reference Example 34) in dimethylformamide (30 ml) was added hydrazine acetate (152 mg, 1.65 mmol) at room temperature under an atmosphere of nitrogen and the mixture was stirred for 1 hour. After checking the completion of the reaction, a solution of p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (814 mg, 1.37 mmol) in acetonitrile (40 ml) was added dropwise to the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (955 μl, 5.48 mmol). The mixture was stirred overnight while gradually raising the temperature to room temperature. After checking the completion of the reaction, ethyl acetate and saturated aqueous sodium hydrogencarbonate solution were added to the reaction mixture. The resulting mixture was shaken in a separatory funnel and the ethyl acetate layer was separated, washed with 10% aqueous sodium chloride solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane: ethyl acetate (1:2) and ethyl acetate as the eluant to afford p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[(1S)-1-(t-butyidimethylsilyloxymethyl)-propylcarbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (928 mg, yield 89%) as a pale yellow solid.

Workup

  1. customthe completion of the reaction
  2. stirringThe mixture was stirred overnight
  3. additionwere added to the reaction mixture
  4. stirringThe resulting mixture was shaken in a separatory funnel
  5. customthe ethyl acetate layer was separated
  6. washwashed with 10% aqueous sodium chloride solution and saturated aqueous sodium chloride solution
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-499eff4442364b53bd8e84a06dc9921d
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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