Uracil → 1-(3-tert-Butyl-5-iodo-4-methoxyphenyl)pyrimidine-2,4(1H,3H)-dione

HRID 2359995Notes

Reaction equation

HRID 2359995 reaction equation
[NH:1]1[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]1=[O:3].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(C1C=CC=CC=1NC(=O)C1C=CC=CN=1)#N.[C:34]([C:38]1[CH:43]=[C:42](I)[CH:41]=[C:40]([I:45])[C:39]=1[O:46][CH3:47])([CH3:37])([CH3:36])[CH3:35]>CS(C)=O.[Cu]I.CC#N>[C:34]([C:38]1[CH:43]=[C:42]([N:1]2[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]2=[O:3])[CH:41]=[C:40]([I:45])[C:39]=1[O:46][CH3:47])([CH3:37])([CH3:35])[CH3:36]

Participants

8

Reactant 4

HCID 1174UracilHCID 62657Potassium Phosphate, TribasicHCID 24700711N-(2-Cyanophenyl)pyridine-2-carboxamideHCID 574194401-(Tert-butyl)-3,5-diiodo-2-methoxybenzene

Product 1

HCID 574938771-(3-tert-Butyl-5-iodo-4-methoxyphenyl)pyrimidine-2,4(1H,3H)-dioneYield 70%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

Uracil (33.3 g, 297 mmol, 1.2 equiv.), K3PO4 (106 g, 500 mmol, 2.1 equiv.), CuI (4.6 g, 24.2 mmol, 0.1 equiv.), and N-(2-cyanophenyl)picolinamide (6.4 g, 28.7 mmol, 0.12 equiv.) were charged to a flask and inerted with argon. The 1-tert-butyl-3,5-diiodo-2-methoxybenzene was solvent switched into MeCN, dissolved in 1 L DMSO and sparged with argon and added to the solids. The reaction was heated to 60° C. for 16 h. After cooling, the reaction was diluted with 2 L EtOAc and washed with 2.6 L water (back extracted with 3×1 L EtOAc). The combined organic layers were washed with 2×1 L of 0.25M (CuOAc)2 then 2×830 mL 15% NH4Cl then 800 mL brine. The organic layer was then concentrated and chased with 1 L heptane, then triturated with refluxing 85:15 (v/v) heptane:iPrOAc for 4 h. After cooling, the product was collected by filtration and washed with an additional 330 mL of 85:15 v/v heptanes:EtOAc to yield after drying 66.9 g (70% yield) of the product as a white solid.

Workup

  1. customsparged with argon
  2. additionadded to the solids
  3. temperatureAfter cooling
  4. additionthe reaction was diluted with 2 L EtOAc
  5. washwashed with 2.6 L water (
  6. extractionback extracted with 3×1 L EtOAc)
  7. washThe combined organic layers were washed with 2×1 L of 0.25M (CuOAc)2
  8. concentrationThe organic layer was then concentrated
  9. customtriturated
  10. temperaturewith refluxing 85:15 (v/v) heptane
  11. temperatureAfter cooling
  12. filtrationthe product was collected by filtration
  13. washwashed with an additional 330 mL of 85:15 v/v heptanes
  14. customEtOAc to yield

Sources & evidence

ORD record
ord-826d5533852648e5b8d1891f1875e6a8
Source dataset
uspto-grants-2014_04
Patent number
US08685991B2

Reaction notes

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