Diisopropylethylamine → HCID 131725323, compound

HRID 891506Notes

Reaction equation

HRID 891506 reaction equation
C([S:4][CH:5]1[CH2:8][N:7]([C:9]2[S:10][CH:11]=[C:12]([C:14](=[O:30])[NH:15][C@H:16]([CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[C@@H:17]([CH3:20])[CH2:18][CH3:19])[N:13]=2)[CH2:6]1)(=O)C.C(O)(=O)C.NN.C1(P(O[C:52]2[C@H:53]([CH3:76])[C@H:54]3[C@@H:71]([C@H:72]([OH:74])[CH3:73])[C:70](=[O:75])[N:55]3[C:56]=2[C:57]([O:59][CH2:60][C:61]2[CH:66]=[CH:65][C:64]([N+:67]([O-:69])=[O:68])=[CH:63][CH:62]=2)=[O:58])(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:23]([O:22][CH2:21][C@@H:16]([NH:15][C:14]([C:12]1[N:13]=[C:9]([N:7]2[CH2:6][CH:5]([S:4][C:52]3[C@H:53]([CH3:76])[C@@H:54]4[C@@H:71]([C@H:72]([OH:74])[CH3:73])[C:70](=[O:75])[N:55]4[C:56]=3[C:57]([O:59][CH2:60][C:61]3[CH:62]=[CH:63][C:64]([N+:67]([O-:69])=[O:68])=[CH:65][CH:66]=3)=[O:58])[CH2:8]2)[S:10][CH:11]=1)=[O:30])[C@@H:17]([CH3:20])[CH2:18][CH3:19])([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 165591Hydrazine, acetate (1:1)HCID 516892Sodium BicarbonateHCID 58595084HCID 58595084, compoundHCID 131720384p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131725323HCID 131725323, compoundYield 51.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-acetylthio-1-{4-[(1S,2S)-1-(t-butyldimethylsilyloxymethyl)-2-methylbutylcarbamoyl]-1,3-thiazol-2-yl}azetidine (910 mg, 1.93 mmol) (obtained as described in Reference Example 38) in dimethylformamide (46 ml) was added hydrazine acetate (213 mg, 2.31 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 (1.15 g, 1.93 mmol) in acetonitrile (58 ml) was added dropwise into the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (1.34 ml, 7.72 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 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: n-hexane: ethyl acetate (1:1→1:4)) to afford p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[(1S,2S)-1-(t-butyldimethylsilyloxymethyl)-2-methylbutylcarbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (765 mg, yield 51%) 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 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: n-hexane: ethyl acetate (1:1→1:4))

Sources & evidence

ORD record
ord-07c7e4556fed4b7da5dfe4dc82e7e9e8
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

Loading…