Hydrochloric Acid → 2-(4-{4-[3-(3-Cyclohexylureido)-3-Oxopropyl]-Phenoxy}-Phenyl)-3-(3,5-Dimethoxyphenyl)-Acrylic Acid

HRID 2253274Notes

Reaction equation

HRID 2253274 reaction equation
[CH:1]1([NH:7][C:8]([NH2:10])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:11][O:12][C:13]1[CH:14]=[C:15]([CH:21]=[C:22]([C:26]2[CH:31]=[CH:30][C:29]([O:32][C:33]3[CH:38]=[CH:37][C:36]([CH2:39][CH2:40][C:41](OCC)=[O:42])=[CH:35][CH:34]=3)=[CH:28][CH:27]=2)[C:23]([OH:25])=[O:24])[CH:16]=[C:17]([O:19][CH3:20])[CH:18]=1.C(O)(C(F)(F)F)=O.Cl>[O-]CC.[Na+].C(O)C>[CH:1]1([NH:7][C:8](=[O:9])[NH:10][C:41](=[O:42])[CH2:40][CH2:39][C:36]2[CH:35]=[CH:34][C:33]([O:32][C:29]3[CH:28]=[CH:27][C:26]([C:22](=[CH:21][C:15]4[CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]([O:12][CH3:11])[CH:14]=4)[C:23]([OH:25])=[O:24])=[CH:31][CH:30]=3)=[CH:38][CH:37]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 69684CyclohexylureaHCID 69131096HCID 69131096, compound

Product 1

HCID 691302652-(4-{4-[3-(3-Cyclohexylureido)-3-Oxopropyl]-Phenoxy}-Phenyl)-3-(3,5-Dimethoxyphenyl)-Acrylic Acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 2723922Sodium ethoxideSolvent

Conditions

Temperature
75 °C

Procedure

Cyclohexylurea (1.3 g, 9 mmol) was dissolved in sodium ethoxide in ethanol (21% w/w, 3 mL) at 75° C. To this solution 5 was added (0.5 g, 1.1 mmol) in one lot. The resulting mixture was stirred at 75° C. for 5 min, then cooled quickly to 40-50° C. TFA (0.5 mL) was added and then 5% aqueous HCl (1N, 0.6 mL). After stirring at room temperature for 1 hr, the mixture was left overnight at 4° C. The solid separated was filtered and refluxed in ethyl acetate (4 mL) for 20 min. The mixture was allowed to cool to room temperature, filtered and the crude product was purified by silica gel chromatography using hexane-ethyl acetate (1:1). Yield: 0.27 g, 45%.

Workup

  1. temperaturecooled quickly to 40-50° C
  2. stirringAfter stirring at room temperature for 1 hr
  3. waitthe mixture was left overnight at 4° C
  4. customThe solid separated
  5. filtrationwas filtered
  6. temperaturerefluxed in ethyl acetate (4 mL) for 20 min
  7. temperatureto cool to room temperature
  8. filtrationfiltered
  9. customthe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-5b6832600898468d80bc84d955293681
Source dataset
uspto-grants-2008_01
Patent number
US07323496B2

Reaction notes

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