Acetic Acid → HCID 13457166, compound

HRID 462446Notes

Reaction equation

HRID 462446 reaction equation
[CH3:1][C:2]1[N:3]([CH2:9][CH2:10][O:11][CH2:12][C:13](=O)[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:4]([CH3:8])=[C:5]([CH3:7])[N:6]=1.[Cl:21][C:22]1[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=1[CH:24]=O.[NH2:30]/[C:31](/[CH3:37])=[CH:32]\[C:33]([O:35][CH3:36])=[O:34].C(O)(=O)C>C(O)C>[ClH:21].[Cl:21][C:22]1[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=1[CH:24]1[C:32]([C:33]([O:35][CH3:36])=[O:34])=[C:31]([CH3:37])[NH:30][C:13]([CH2:12][O:11][CH2:10][CH2:9][N:3]2[C:4]([CH3:8])=[C:5]([CH3:7])[N:6]=[C:2]2[CH3:1])=[C:14]1[C:15]([O:17][CH2:18][CH3:19])=[O:16]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 69962-ChlorobenzaldehydeHCID 643918Methyl 3-aminocrotonateHCID 13457163HCID 13457163, compound

Product 1

HCID 13457166HCID 13457166, compoundYield 19.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Ethyl 4-[2-(2,4,5-trimethyl-1-imidazolyl)ethoxy]acetoacetate (6.4 g), 2-chlorobenzaldehyde (3.2 g), methyl 3-aminocrotonate (2.6 g) and acetic acid (1 ml) in ethanol (15 ml) were mixed and heated under reflux for 4.5 hours. The cooled reaction mixture was then evaporated to dryness and the residue partitioned between 2N hydrochloric acid (100 ml) and toluene (50 ml). The acid layer was separated, extracted with methylene chloride (3×20 ml) and the extracts were washed with saturated aqueous sodium carbonate (30 ml), dried (Na2CO3), filtered, and evaporated. The residue in a little toluene was chromatographed on silica (t.l.c. grade, 4 g), eluting with methylene chloride plus 30% v/v petrol. Appropriate fractions were combined, evaporated to dryness and redissolved in ethyl acetate. Addition of ethereal hydrogen chloride precipitated the hydrochloride salt, which was recrystllised from ethyl acetate to give the title compound (1.2 g), m.p. 167°-8° C.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 4.5 hours
  3. customThe cooled reaction mixture
  4. customwas then evaporated to dryness
  5. customthe residue partitioned between 2N hydrochloric acid (100 ml) and toluene (50 ml)
  6. customThe acid layer was separated
  7. extractionextracted with methylene chloride (3×20 ml)
  8. washthe extracts were washed with saturated aqueous sodium carbonate (30 ml)
  9. dry with materialdried (Na2CO3)
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue in a little toluene was chromatographed on silica (t.l.c. grade, 4 g)
  13. washeluting with methylene chloride plus 30% v/v petrol
  14. customevaporated to dryness
  15. dissolutionredissolved in ethyl acetate
  16. additionAddition of ethereal hydrogen chloride
  17. customprecipitated the hydrochloride salt, which

Sources & evidence

ORD record
ord-cf96821e87af49a8b72cf2045f983bd9
Source dataset
uspto-grants-1985_05
Patent number
US04515799

Reaction notes

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