Methanol → 5-Hexyl-5-(4-phenoxy-phenyl)-pyrimidine-2,4,6-trione

HRID 1386644Notes

Reaction equation

HRID 1386644 reaction equation
CO.[H][H].[O:5]([C:12]1[CH:17]=[CH:16][C:15]([C:18]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])([C:23](OC)=[O:24])[C:19](OC)=[O:20])=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[NH2:33][C:34]([NH2:36])=[O:35]>C(Cl)(Cl)(Cl)Cl.CCOC(C)=O>[CH2:27]([C:18]1([C:15]2[CH:14]=[CH:13][C:12]([O:5][C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)=[CH:17][CH:16]=2)[C:23](=[O:24])[NH:36][C:34](=[O:35])[NH:33][C:19]1=[O:20])[CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]

Participants

7

Reactant 4

HCID 887MethanolHCID 1176UreaHCID 21183037Dimethyl 2-(4-phenoxyphenyl)-2-n-hexylmalonateHCID 178418361HCID 178418361, compound

Product 1

HCID 98861775-Hexyl-5-(4-phenoxy-phenyl)-pyrimidine-2,4,6-trioneYield 66.7%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Mg(OCH3)2was prepared as follows: To a 25 mL round-bottom flask under argon was added Mg tunings (90 mg, 3.70 mmol), dry CH3OH (2 mL), 2 drops of CCl4 and a catalytic amount of Mg powder. An exothermic reaction took place and hydrogen gas evolution was observed. After the initial exothermic reaction subsided, the reaction mixture was heated to reflux for 1 hour and then cooled to room temperature. Dimethyl 2-(4-phenoxyphenyl)-2-n-hexylmalonate (500 mg, 1.30 mmol) and urea (162 mg, 2.70 mmol) were added to the Mg(OCH3)2. The reaction mixture was heated at 85-90° C. for 1 hour and then excess CH3OH was distilled off until a fluid-paste was obtained and this paste was then heated at 85-90° C. overnight. The reaction was cooled to room temperature, diluted with EtOAc, and washed with 1N HCl. The acidic aqueous layer was re-extracted with EtOAc. The combined EtOAc extracts were washed with water, brine, dried (MgSO4), and concentrated. The resulting oil was purified with HPLC (porasil) using 30% EtOAc/hexanes as eluent to afford 330 mg of 5-n-hexyl-5-(4-phenoxyphenyl)pyrimidine-2,4,6-trione as a white foam: 1H NMR (400 mHz DMSO-d6) δ 11.71 (2NH, s), 7.42-6.99 (9H, m), 2.22 (2H, t), 1.24 (8H, m), 0.85 (3H, t); HRMS Calcd for C22H24N2O4 380.1736; Found 380.1740.

Workup

  1. customAn exothermic reaction
  2. customAfter the initial exothermic reaction
  3. temperaturethe reaction mixture was heated
  4. temperatureto reflux for 1 hour
  5. temperatureThe reaction mixture was heated at 85-90° C. for 1 hour
  6. distillationexcess CH3OH was distilled off until a fluid-paste
  7. customwas obtained
  8. temperaturethis paste was then heated at 85-90° C. overnight
  9. temperatureThe reaction was cooled to room temperature
  10. washwashed with 1N HCl
  11. extractionThe acidic aqueous layer was re-extracted with EtOAc
  12. washThe combined EtOAc extracts were washed with water, brine
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated
  15. customThe resulting oil was purified with HPLC (porasil)

Sources & evidence

ORD record
ord-24cf1c375ead4f929f8046a4d2b42a23
Source dataset
uspto-grants-2001_07
Patent number
US06265578B1

Reaction notes

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