Diisopropylethylamine → HCID 131725319, compound

HRID 891503Notes

Reaction equation

HRID 891503 reaction equation
C([S:4][CH:5]1[CH2:8][N:7]([C:9]2[S:10][CH:11]=[C:12]([C:14](=[O:29])[NH:15][C@H:16]([CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH:17]([CH3:19])[CH3:18])[N:13]=2)[CH2:6]1)(=O)C.C(O)(=O)C.NN.C1(P(O[C:51]2[C@H:52]([CH3:75])[C@H:53]3[C@@H:70]([C@H:71]([OH:73])[CH3:72])[C:69](=[O:74])[N:54]3[C:55]=2[C:56]([O:58][CH2:59][C:60]2[CH:65]=[CH:64][C:63]([N+:66]([O-:68])=[O:67])=[CH:62][CH:61]=2)=[O:57])(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:22]([O:21][CH2:20][C@@H:16]([NH:15][C:14]([C:12]1[N:13]=[C:9]([N:7]2[CH2:8][CH:5]([S:4][C:51]3[C@H:52]([CH3:75])[C@@H:53]4[C@@H:70]([C@H:71]([OH:73])[CH3:72])[C:69](=[O:74])[N:54]4[C:55]=3[C:56]([O:58][CH2:59][C:60]3[CH:61]=[CH:62][C:63]([N+:66]([O-:68])=[O:67])=[CH:64][CH:65]=3)=[O:57])[CH2:6]2)[S:10][CH:11]=1)=[O:29])[CH:17]([CH3:19])[CH3:18])([C:25]([CH3:27])([CH3:28])[CH3:26])([CH3:23])[CH3:24]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 165591Hydrazine, acetate (1:1)HCID 516892Sodium BicarbonateHCID 58595117HCID 58595117, compoundHCID 131720384p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131725319HCID 131725319, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-acetylthio-1-{4-[(1S)-1-(t-butyldimethylsilyloxymethyl)-2-methyl-propylcarbamoyl]-1,3-thiazol-2-yl}azetidine (500 mg, 1.09 mmol) (obtained as described in Reference Example 36) in dimethylformamide (25 ml) was added hydrazine acetate (121 mg, 1.31 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 (648 mg, 1.09 mmol) in acetonitrile (33 ml) was added dropwise to the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (759 μl, 4.36 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 1:4) as the eluant to afford p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[(1S)-1-(t-butyldimethylsilyloxymethyl)-2-methyl-propylcarbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (649 mg, yield 84%) 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-b42522cb447341d48ac28eeaea0c3526
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

Loading…