Diisopropylethylamine → HCID 131725338, compound

HRID 891520Notes

Reaction equation

HRID 891520 reaction equation
C([S:4][CH:5]1[CH2:8][N:7]([C:9]2[S:10][CH:11]=[C:12]([C:14](=[O:33])[NH:15][CH:16]3[CH2:19][N:18]([C:20]([O:22][CH2:23][C:24]4[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=4)=[O:21])[CH2:17]3)[N:13]=2)[CH2:6]1)(=O)C.C(O)(=O)C.NN.C1(P(O[C:55]2[C@H:56]([CH3:79])[C@H:57]3[C@@H:74]([C@H:75]([OH:77])[CH3:76])[C:73](=[O:78])[N:58]3[C:59]=2[C:60]([O:62][CH2:63][C:64]2[CH:69]=[CH:68][C:67]([N+:70]([O-:72])=[O:71])=[CH:66][CH:65]=2)=[O:61])(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>[N+:30]([C:27]1[CH:28]=[CH:29][C:24]([CH2:23][O:22][C:20]([N:18]2[CH2:19][CH:16]([NH:15][C:14]([C:12]3[N:13]=[C:9]([N:7]4[CH2:8][CH:5]([S:4][C:55]5[C@H:56]([CH3:79])[C@@H:57]6[C@@H:74]([C@H:75]([OH:77])[CH3:76])[C:73](=[O:78])[N:58]6[C:59]=5[C:60]([O:62][CH2:63][C:64]5[CH:65]=[CH:66][C:67]([N+:70]([O-:72])=[O:71])=[CH:68][CH:69]=5)=[O:61])[CH2:6]4)[S:10][CH:11]=3)=[O:33])[CH2:17]2)=[O:21])=[CH:25][CH:26]=1)([O-:32])=[O:31]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 165591Hydrazine, acetate (1:1)HCID 516892Sodium BicarbonateHCID 17858126HCID 17858126, compoundHCID 131720384p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131725338HCID 131725338, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-acetylthio-1-{4-[1-(p-nitrobenzyloxycarbonyl)-azetidin-3-ylcarbamoyl]-1,3-thiazol-2-yl}azetidine (400 mg, 0.814 mmol) (obtained as described in Reference Example 54) in dimethylformamide (20 ml) was added hydrazine acetate (90 mg, 0.977 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 (484 mg, 0.814 mmol) in acetonitrile (25 ml) was added dropwise into the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (568 μl, 3.26 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 0.5 M hydrochloric acid, saturated aqueous sodium hydrogencarbonate 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 (9:1)) to afford p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[1-(p-nitrobenzyloxycarbonyl)-azetidin-3-ylcarbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (496 mg, yield 77%) 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 0.5 M hydrochloric acid, saturated aqueous sodium hydrogencarbonate 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 (9:1))

Sources & evidence

ORD record
ord-d5ecd34ed2214c639a4cf1b6e8a7fbdc
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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