Ethyl 2-chloroacetoacetate → HCID 14500718, compound

HRID 2350894Notes

Reaction equation

HRID 2350894 reaction equation
[CH2:1]([NH:6][C:7](=S)[NH:8][NH2:9])[CH2:2][CH2:3][CH2:4][CH3:5].Cl[CH:12]([C:18]([CH3:20])=O)[C:13]([O:15][CH2:16][CH3:17])=[O:14]>O1CCCC1>[CH3:20][C:18]1[NH:9][N:8]=[C:7]([NH:6][CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])[C:12]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14]

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 2513311N-pentylhydrazinecarbothioamide

Product 1

HCID 14500718HCID 14500718, compoundYield 20.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 25.8 g (0.16 mole) of 4-pentyl-3-thiosemicarbazide in 150 mL of tetrahydrofuran was treated with 26.4 g (0.16 mole) of ethyl 2-chloroacetoacetate, stirred at ambient temperature for 2 hr, heated at reflux for 4 hr, and stirred for ~16 hr at ambient temperature. The reaction mixture contained amorphous material and large yellow crystals, which dissolved on heating at reflux for 1 hr. Upon cooling, large yellow crystals separated and were removed by filtration (sulfur). The filtrate was diluted with ice water, made acidic with 6N sulfuric acid and filtered to remove additional sulfur. The filtrate was adjusted to pH 6 with sodium carbonate and a total of 32.2 g of precipitated product was collected in 3 fractions. All the material was chromatographed twice on silica gel without purification, first by eluting with methylene chloride and the second time by eluting with benzene. A third column of 800 g of silica gel was eluted with isopropyl ether to give an orange oil which was not the product, then eluted with 50/50 isopropyl ether/methylene chloride. The product crystallized from the second eluent to give 7.8 g of white crystalline product after washing with isopropyl ether to remove a yellow color, mp 117°-119° C.

Workup

  1. temperatureheated
  2. temperatureat reflux for 4 hr
  3. stirringstirred for ~16 hr at ambient temperature
  4. dissolutiondissolved
  5. temperatureon heating
  6. temperatureat reflux for 1 hr
  7. temperatureUpon cooling
  8. customlarge yellow crystals separated
  9. customwere removed by filtration (sulfur)
  10. additionThe filtrate was diluted with ice water
  11. filtrationfiltered
  12. customto remove additional sulfur
  13. customa total of 32.2 g of precipitated product was collected in 3 fractions
  14. customAll the material was chromatographed twice on silica gel without purification
  15. washfirst by eluting with methylene chloride
  16. washthe second time by eluting with benzene
  17. washA third column of 800 g of silica gel was eluted with isopropyl ether
  18. customto give an orange oil which
  19. washeluted with 50/50 isopropyl ether/methylene chloride
  20. customThe product crystallized from the second eluent

Sources & evidence

ORD record
ord-31eaf1372a0b499aa135c9673b9f7623
Source dataset
uspto-grants-1989_10
Patent number
US04871737

Reaction notes

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