Diisopropylethylamine → HCID 131725333, compound

HRID 891512Notes

Reaction equation

HRID 891512 reaction equation
C([S:4][CH:5]1[CH2:8][N:7]([C:9]2[S:10][CH:11]=[C:12]([C:14](=[O:23])[N:15]([CH2:19][C:20](=[O:22])[NH2:21])[CH:16]([CH3:18])[CH3:17])[N:13]=2)[CH2:6]1)(=O)C.C(O)(=O)C.NN.C1(P(O[C:45]2[C@H:46]([CH3:69])[C@H:47]3[C@@H:64]([C@H:65]([OH:67])[CH3:66])[C:63](=[O:68])[N:48]3[C:49]=2[C:50]([O:52][CH2:53][C:54]2[CH:59]=[CH:58][C:57]([N+:60]([O-:62])=[O:61])=[CH:56][CH:55]=2)=[O:51])(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.CO.C(OCC)(=O)C>[C:20]([CH2:19][N:15]([CH:16]([CH3:18])[CH3:17])[C:14]([C:12]1[N:13]=[C:9]([N:7]2[CH2:6][CH:5]([S:4][C:45]3[C@H:46]([CH3:69])[C@@H:47]4[C@@H:64]([C@H:65]([OH:67])[CH3:66])[C:63](=[O:68])[N:48]4[C:49]=3[C:50]([O:52][CH2:53][C:54]3[CH:59]=[CH:58][C:57]([N+:60]([O-:62])=[O:61])=[CH:56][CH:55]=3)=[O:51])[CH2:8]2)[S:10][CH:11]=1)=[O:23])(=[O:22])[NH2:21]

Participants

10

Reactant 5

HCID 81531DiisopropylethylamineHCID 165591Hydrazine, acetate (1:1)HCID 516892Sodium BicarbonateHCID 22243075HCID 22243075, compoundHCID 131720384p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131725333HCID 131725333, compoundYield 56.2%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

To a solution of 3-acetylthio-1-[4-(N-carbamoylmethyl-N-isopropyl-carbamoyl)-1,3-thiazol-2-yl]azetidine (347 mg, 0.97 mmol) (obtained as described in Reference Example 49) in dimethylformamide (10 ml) was added hydrazine acetate (108 mg, 1.17 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 (696 mg,1.17 mmol) in acetonitrile (20 ml) was added dropwise into the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (0.68 ml, 3.88 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 magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column (eluant: ethyl acetate: methanol (10:1) to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(N-carbamoylmethyl-N-isopropyl-carbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (359 mg, yield 56%) 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 magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography on a silica gel column (eluant

Sources & evidence

ORD record
ord-3739ee9794cd484e9ba66072b777da7f
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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