Acetic Acid → HCID 54739236, compound

HRID 2046267Notes

Reaction equation

HRID 2046267 reaction equation
[CH:1]1([C:7](=[N:13][NH:14][C:15](=[O:22])[CH2:16][C:17]([O:19]CC)=O)[C:8]([O:10]CC)=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:23]1([Mg]Br)CC[CH2:26][CH2:25][CH2:24]1.C(OC(=O)CC([NH:38]N)=O)C.[CH3:41][C:42]([OH:44])=[O:43].[CH2:45]1[CH2:49]O[CH2:47][CH2:46]1>>[CH:1]1([C:7]2[C:8]([OH:10])=[C:16]([C:17]([NH:38][CH2:41][C:42]([OH:44])=[O:43])=[O:19])[C:15](=[O:22])[N:14]([CH2:47][C:46]3[CH:26]=[CH:25][CH:24]=[CH:23][C:45]=3[CH3:49])[N:13]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 252897Ethyl 3-hydrazino-3-oxopropionateHCID 72575856HCID 72575856, compoundHCID 178419651HCID 178419651, compound

Product 1

HCID 54739236HCID 54739236, compoundYield 21%

Conditions

Temperature
-78 °C

Procedure

Ethyl 3-{2-[1-cyclohexyl-2-(ethyloxy)-2-oxoethylidene]hydrazino}-3-oxopropanoate. A solution of diethyl oxylate (4.1 mL, 30.0 mmol) in THF (50 mL) was cooled to −78° C. Cyclohexyl magnesium bromide (1.0M solution in THF, 36 mL, 36.0 mmol) was dropwise added and the solution stirred under a nitrogen atmosphere for 1.5 h at −78° C. The reaction was brought to 0° C. and quenched with 6N HCl. Et2O and H2O were added and the layers separated. The aqueous phase was backextracted with Et2O several times. The combined organic layers were washed with Brine, dried (MgSO4), filtered and concentrated. The resulting residue was dissolved in EtOH (20 mL) and partitioned between two microwave vials. Ethyl-3-hydrazino-3-oxopropionate (2.41 g, 18.0 mmol) and catalytic AcOH (0.2 mL, 3.50 mmol) were added to each vial. The reactions were heated in the microwave at 150° C. for 1 h. The reactions were cooled and combined in a round bottom flask. The solvent was removed under reduced pressure and the resulting residue was azeotroped with Toluene several times. The product was purified by column chromatography (SiO2, 10-30% EtOAc/Hexanes) to give the title compound (1.93 g, 21% over 2 steps). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.44-11.78 (m, 1H) 3.99-4.34 (m, 4H) 3.44-3.67 (m, 2H) 2.52-2.63 (m, 1H) 1.52-1.84 (m, 5H) 1.04-1.37 (m, 11H).

Workup

  1. customwas brought to 0° C.
  2. customquenched with 6N HCl
  3. additionEt2O and H2O were added
  4. customthe layers separated
  5. washThe combined organic layers were washed with Brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe resulting residue was dissolved in EtOH (20 mL)
  10. custompartitioned between two microwave vials
  11. temperatureThe reactions were heated in the microwave at 150° C. for 1 h
  12. temperatureThe reactions were cooled
  13. customcombined in a round bottom flask
  14. customThe solvent was removed under reduced pressure
  15. customthe resulting residue was azeotroped with Toluene several times
  16. customThe product was purified by column chromatography (SiO2, 10-30% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-6d2022dc9f814fd5ab0c9a5874594305
Source dataset
uspto-grants-2013_11
Patent number
USRE044613E1

Reaction notes

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