Diisopropylethylamine → HCID 131725334, compound

HRID 891513Notes

Reaction equation

HRID 891513 reaction equation
C([S:4][CH:5]1[CH2:8][N:7]([C:9]2[S:10][CH:11]=[C:12]([C:14](=[O:22])[N:15]([CH2:19][C:20]#[N:21])[CH:16]([CH3:18])[CH3:17])[N:13]=2)[CH2:6]1)(=O)C.C(O)(=O)C.NN.C1(P(O[C:44]2[C@H:45]([CH3:68])[C@H:46]3[C@@H:63]([C@H:64]([OH:66])[CH3:65])[C:62](=[O:67])[N:47]3[C:48]=2[C:49]([O:51][CH2:52][C:53]2[CH:58]=[CH:57][C:56]([N+:59]([O-:61])=[O:60])=[CH:55][CH:54]=2)=[O:50])(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>[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:44]3[C@H:45]([CH3:68])[C@@H:46]4[C@@H:63]([C@H:64]([OH:66])[CH3:65])[C:62](=[O:67])[N:47]4[C:48]=3[C:49]([O:51][CH2:52][C:53]3[CH:54]=[CH:55][C:56]([N+:59]([O-:61])=[O:60])=[CH:57][CH:58]=3)=[O:50])[CH2:8]2)[S:10][CH:11]=1)=[O:22])#[N:21]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 165591Hydrazine, acetate (1:1)HCID 516892Sodium BicarbonateHCID 22242720HCID 22242720, compoundHCID 131720384p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131725334HCID 131725334, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 3-acetylthio-1-[4-(N-cyanomethyl-N-isopropyl-carbamoyl)-1,3-thiazol-2-yl]azetidine (344 mg, 1.01 mmol) (obtained as described in Reference Example 50) in dimethylformamide (1 0 ml) was added hydrazine acetate (112 mg, 1.22 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 (725 mg, 1.22 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 (0.70 ml, 4.04 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→ethyl acetate:methanol (10:1) to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(N-cyanomethyl-N-isopropyl-carbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (245 mg, yield 39%) 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-c5d291f62d8a4f90b49a8b3c59b159a4
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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