Reaction #1973955

Reaction equation

1-tert-butyl-3,5-diiodo-2-methoxybenzene

Uracil

K3PO4

N-(2-cyanophenyl)picolinamide

→

product

Yield 70.0%

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

Yield 70.0%

Solvents

MeCN

DMSO

Conditions

Workup

1. 1
   Othersparged with argon
2. 2
   workup.ADDITIONadded to the solids
3. 3
   TemperatureAfter cooling
4. 4
   workup.ADDITIONthe reaction was diluted with 2 L EtOAc
5. 5
   Washwashed with 2.6 L water (
6. 6
   Extractionback extracted with 3×1 L EtOAc)
7. 7
   WashThe combined organic layers were washed with 2×1 L of 0.25M (CuOAc)2
8. 8
   ConcentrationThe organic layer was then concentrated
9. 9
   Othertriturated
10. 10
    Temperaturewith refluxing 85:15 (v/v) heptane
11. 11
    TemperatureAfter cooling
12. 12
    Filtrationthe product was collected by filtration
13. 13
    Washwashed with an additional 330 mL of 85:15 v/v heptanes
14. 14
    OtherEtOAc to yield

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.

Source