Hydrochloric Acid → HCID 59016024, compound

HRID 968829Notes

Reaction equation

HRID 968829 reaction equation
[O-]CC.[Na+].C(OCC)(=O)C.[OH:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][CH2:20][C:21]2[N:22]([CH2:35][CH2:36][CH3:37])[C:23](=[O:34])[N:24]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=3)[N:25]=2)=[CH:14][CH:13]=1.[C:38]([O:43][CH:44](CC)[CH2:45]CC)(=[O:42])[CH:39]([CH3:41])[CH3:40].Cl>C(O)C.O.C(OC(CC)CCC)(=O)C(C)C>[CH2:44]([O:43][C:38](=[O:42])[C:39]([CH3:41])([O:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][CH2:20][C:21]2[N:22]([CH2:35][CH2:36][CH3:37])[C:23](=[O:34])[N:24]([CH2:26][C:27]3[CH:28]=[CH:29][C:30]([CH3:33])=[CH:31][CH:32]=3)[N:25]=2)=[CH:14][CH:13]=1)[CH3:40])[CH3:45]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 2723922Sodium ethoxide5×HCID 58579265Ethyl-2-butyl isobutyrate3×HCID 59015891HCID 59015891, compound

Product 1

HCID 59016024HCID 59016024, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 58579265Ethyl-2-butyl isobutyrateCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a mixture of sodium ethoxide (1.22 mL, 3.28 mmol) and ethyl acetate (322 μL, 3.28 mmol) was added 5-[3-(4-hydroxyphenyl)-propyl]-2-(4-methylbenzyl)-4-propyl-2,4-dihydro-[1,2,4]triazol-3-one (1.2 g, 3.28 mmol) in ethanol (10 mL) and the resulting mixture stirred at reflux for 1 hour. Then ethyl-2-butyl isobutyrate (1.08 mL, 7.38 mmol) was added and the reaction continued at reflux for 1 hour. Then sodium ethoxide (1.22 mL, 3.28 mmol) was added dropwise over 5 min and the reaction continued at reflux for 4.5 hour. Additional sodium ethoxide (520 μL, 1.4 mmol) and ethyl-2-butyl isobutyrate (205 μL, 1.4 mmol) were added and reaction continued at reflux for 4 hour. Additional sodium ethoxide (336 μL, 0.903 mmol) and ethyl-2-butyl isobutyrate (132 μL, 0.903 mmol) were added and the reaction continued at reflux for 3 hours. Finally, additional sodium ethoxide (200 μL, 0.54 mmol) and ethyl-2-butyl isobutyrate (100 μL, 0.133 mmol) were added and the reaction continued at reflux for 1.5 hours. The mixture was allowed to cool to room temperature and is then quenched into a solution of conc. HCl (1.5 g, 41 mmol) in water (50 mL). The resulting solution was then concentrated in vacuo, taken up in ethyl acetate (100 mL) and the aqueous layer was discarded. The organic layer was washed with saturated aq. NaHCO3 (2×50 mL) followed by saturated aq. NaCl (2×25 mL). The organic layer was dried (MgSO4), filtered, concentrated, and purified by silica gel chromatography (1:1 ethyl acetate:hexanes) to afford the title compound as a yellow oil (990 mg, 2.06 mmol, 63%):

Workup

  1. temperatureat reflux for 1 hour
  2. temperatureat reflux for 1 hour
  3. temperatureat reflux for 4.5 hour
  4. customreaction
  5. temperatureat reflux for 4 hour
  6. temperatureat reflux for 3 hours
  7. temperatureat reflux for 1.5 hours
  8. concentrationThe resulting solution was then concentrated in vacuo
  9. washThe organic layer was washed with saturated aq. NaHCO3 (2×50 mL)
  10. dry with materialThe organic layer was dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. custompurified by silica gel chromatography (1:1 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-678a312068fe442b9c7941984493004d
Source dataset
uspto-grants-2007_12
Patent number
US07304062B2

Reaction notes

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