Water → HCID 19429354, compound

HRID 1078381Notes

Reaction equation

HRID 1078381 reaction equation
[CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.[H-].[Na+].Cl[CH2:10][CH2:11][C:12]([NH:14][CH:15]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)[CH3:16])=[O:13].O>O1CCCC1.C(OCC)(=O)C>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([CH:15]([NH:14][C:12](=[O:13])[CH2:11][CH2:10][N:3]2[CH:4]=[CH:5][N:6]=[C:2]2[CH3:1])[CH3:16])=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 962WaterHCID 127492-MethylimidazoleHCID 24758Sodium hydrideHCID 19429448HCID 19429448, compound

Product 1

HCID 19429354HCID 19429354, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-methylimidazole (2.64 g) in dry tetrahydrofuran (THF) (40 ml ) was added over 1 minute to a stirred suspension of sodium hydride (1.54 g; 60% dispersion in oil) in THF (65 ml) under dry nitrogen. The mixture was stirred at ambient temperature for 1 hour, then heated to boiling under reflux and allowed to cool. A solution of 3-chloro-N-[1-(4-chlorophenyl)ethyl]-propionamide (5.7 g) in THF (25 ml) was added and the mixture stirred under reflux for 16 hours. The mixture was cooled and water (100 ml) was added portion-wise with stirring followed by ethyl acetate (200 ml). The acidic layer was separated and extracted with ethyl acetate and the combined ethyl acetate extracts extracted with hydrochloric acid (5M). The combined acidic extracts were basified with concentrated sodium hydroxide solution and extracted with ethyl acetate to give an oil. The oil was triturated with ether and filtered to give N-[1-(4-chlorophenyl)ethyl]-3-(2-methylimidazol-1-yl)propionamide, m.p. 135°-137° C.

Workup

  1. temperatureheated
  2. temperatureunder reflux
  3. temperatureto cool
  4. stirringthe mixture stirred
  5. temperatureunder reflux for 16 hours
  6. temperatureThe mixture was cooled
  7. stirringwith stirring
  8. customThe acidic layer was separated
  9. extractionextracted with ethyl acetate
  10. extractionthe combined ethyl acetate extracts extracted with hydrochloric acid (5M)
  11. extractionextracted with ethyl acetate
  12. customto give an oil
  13. customThe oil was triturated with ether
  14. filtrationfiltered

Sources & evidence

ORD record
ord-04b280c5c0c9494fa120ae3e2d695c8f
Source dataset
uspto-grants-1996_08
Patent number
US05547972

Reaction notes

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