Hydrochloric Acid → HCID 54749146, compound

HRID 1822372Notes

Reaction equation

HRID 1822372 reaction equation
C(O[C:4](=[O:24])[C:5](=[N:7][N:8]([C:16](=[O:23])[CH2:17][C:18]([O:20]CC)=O)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:6])C.[C:25]([O:30]CC)(=[O:29])[C:26](C)=O.Cl.Cl.C([NH:42]N)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C.ClC(=O)CC(OCC)=O.[H-].[Na+].Cl>ClCCl.S([O-])([O-])(=O)=O.[Mg+2]>[OH:24][C:4]1[C:5]([CH3:6])=[N:7][N:8]([CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:16](=[O:23])[C:17]=1[C:18]([NH:42][CH2:26][C:25]([OH:30])=[O:29])=[O:20]

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 12041Ethyl pyruvate2×HCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 118931Ethyl 3-chloro-3-oxopropionateHCID 146540Benzylhydrazine dihydrochlorideHCID 86623014HCID 86623014, compound

Product 1

HCID 54749146HCID 54749146, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 24083Sulfuric acid magnesium salt (1:1)Solvent2×

Procedure

Ethyl 3-[2-[2-(ethyloxy)-1-methyl-2-oxoethylidene]-1-(phenylmethyl)hydrazino]-3-oxopropanoate. Ethyl pyruvate (0.324 g, 2.79 mmol) was added to a stirred mixture of benzylhydrazine dihydrochloride (0.551 g, 2.82 mmol), diisopropylethylamine (1.00 mL, 5.74 mmol) and dichloromethane (10 mL). Magnesium sulfate (excess) was added and the mixture stirred 0.5 h, then loaded onto a short column of silica gel and the product eluted (50% ethyl acetate/hexane). After evaporation of the solvent, the crude hydrazone (0.339 g) was dissolved in tetrahydrofuran (20 mL) and sodium hydride (0.075 g of a 60% oil suspension, 1.88 mmol) added with stirring. The mixture was stirred 20 min, then ethyl 3-chloro-3-oxopropionate (0.235 mL, 1.84 mmol) injected dropwise and stirring continued at room temperature 10 min and at 60° C. for 0.5 h. Further sodium hydride (0.075 g of a 60% oil suspension, 1.88 mmol) was added and stirring continued at 65° C. for 0.5 h. The mixture was cooled, poured into 0.1M aqueous hydrochloric acid (100 mL) and extracted with ethyl acetate. The extracts were dried (MgSO4) and evaporated under reduced pressure. Ethyl pyruvate (0.324 g, 2.79 mmol) was added to a stirred mixture of the residue in dichloromethane (10 mL) and magnesium sulfate. After 2 h, the mixture was chromatographed (silica gel, 20-50% ethyl acetate/hexane) to give the title compound (0.205 g, 22%) as a gum. LCMS (ES+) m/z 335 (MH+).

Workup

  1. washthe product eluted (50% ethyl acetate/hexane)
  2. customAfter evaporation of the solvent
  3. dissolutionthe crude hydrazone (0.339 g) was dissolved in tetrahydrofuran (20 mL)
  4. additionsodium hydride (0.075 g of a 60% oil suspension, 1.88 mmol) added
  5. stirringwith stirring
  6. stirringThe mixture was stirred 20 min
  7. stirringstirring
  8. waitcontinued at room temperature 10 min and at 60° C. for 0.5 h
  9. stirringstirring
  10. waitcontinued at 65° C. for 0.5 h
  11. temperatureThe mixture was cooled
  12. extractionextracted with ethyl acetate
  13. dry with materialThe extracts were dried (MgSO4)
  14. customevaporated under reduced pressure
  15. waitAfter 2 h
  16. customthe mixture was chromatographed (silica gel, 20-50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-aabcaf0e40244f1884b87acedd390c1e
Source dataset
uspto-grants-2009_10
Patent number
US07608621B2

Reaction notes

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