Acetic Acid → HCID 13457166, compound

HRID 2290312Notes

Reaction equation

HRID 2290312 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 (Na 2CO3), 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 recrystallised 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. customdried (Na 2CO3)
  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
  18. customwas recrystallised from ethyl acetate

Sources & evidence

ORD record
ord-96bb8ee989664c97815c1b4f9057d659
Source dataset
uspto-grants-1986_10
Patent number
US04616024

Reaction notes

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