Dimethylformamide → HCID 131725360, compound

HRID 891541Notes

Reaction equation

HRID 891541 reaction equation
[C:1]([S:4][CH:5]1[CH2:8][N:7]([C:9]2[O:10][CH:11]=[C:12]([C:14](=[O:34])[NH:15][C@H:16]3[CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=4)=[O:22])[CH2:17]3)[N:13]=2)[CH2:6]1)(=O)[CH3:2].[C:35]([OH:38])(=O)[CH3:36].NN.C1(P(OC2[C@H](C)[C@H]3[C@@H]([C@H](O)C)C(=O)N3C=2[C:61]([O:63][CH2:64][C:65]2[CH:70]=[CH:69][C:68]([N+:71]([O-:73])=[O:72])=[CH:67][CH:66]=2)=[O:62])(C2C=CC=CC=2)=O)C=CC=CC=1.C([N:84]([CH:87]([CH3:89])[CH3:88])CC)(C)C.[C:90](=[O:93])([O-])O.[Na+].[CH3:95]N(C)C=O>C(#N)C.C(OCC)(=O)C>[N+:31]([C:28]1[CH:29]=[CH:30][C:25]([CH2:24][O:23][C:21]([N:18]2[CH2:19][CH2:20][C@H:16]([NH:15][C:14]([C:12]3[N:13]=[C:9]([N:7]4[CH2:6][CH:5]([S:4][C:1]5[C@H:89]([CH3:95])[C@@H:87]6[C@@H:88]([C@H:35]([OH:38])[CH3:36])[C:90](=[O:93])[N:84]6[C:2]=5[C:61]([O:63][CH2:64][C:65]5[CH:66]=[CH:67][C:68]([N+:71]([O-:73])=[O:72])=[CH:69][CH:70]=5)=[O:62])[CH2:8]4)[O:10][CH:11]=3)=[O:34])[CH2:17]2)=[O:22])=[CH:26][CH:27]=1)([O-:33])=[O:32]

Participants

9

Reactant 6

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 165591Hydrazine, acetate (1:1)HCID 516892Sodium BicarbonateHCID 86590890HCID 86590890, compoundHCID 131720384p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131725360HCID 131725360, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-acetylthio-1-{4-[(3S)-1-(p-nitrobenzyloxycarbonyl)-pyrrolidin-3-ylcarbamoyl]-1,3-oxazol-2-yl}azetidine (530 mg, 1.08 mmol) (obtained as described in Reference Example 76) in dimethylformamide (27 ml) was added hydrazine acetate (120 mg, 1.30 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 (642 mg, 1.08 mmol) in acetonitrile (32 ml) was added dropwise into the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (753 μl, 4.32 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% 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 (eluant: ethyl acetate→ethyl acetate:methanol (95:5)) to afford p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[(3S)-1-(p-nitrobenzyloxycarbonyl)-pyrrolidin-3-ylcarbamoyl]-1,3-oxazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (652 mg, yield 76%) 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% 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 (eluant: ethyl acetate→ethyl acetate:methanol (95:5))

Sources & evidence

ORD record
ord-7a5d81e1efb6454b9d4df088718e9271
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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