Triethylamine → 3-(4-Chloro-6-Fluoro-2-Phenylbenzofuran-7-yl)-1-Methyl-6-Trifluoromethyl-2,4(1H,3H)-Pyrimidinedione

HRID 1421468Notes

Reaction equation

HRID 1421468 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])=[C:4]([OH:22])[C:3]=1I.[C:24]1([C:30]#[CH:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C.[Cl-].[NH4+]>CN(C=O)C.[Cu]I>[Cl:1][C:2]1[C:3]2[CH:31]=[C:30]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[O:22][C:4]=2[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])=[C:6]([F:8])[CH:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 25517Ammonium ChlorideHCID 183150693-(4-chloro-6-fluoro-2-hydroxy-3-iodophenyl)-1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 183150843-(4-Chloro-6-Fluoro-2-Phenylbenzofuran-7-yl)-1-Methyl-6-Trifluoromethyl-2,4(1H,3H)-PyrimidinedioneYield 23.6%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Under a nitrogen atmosphere, a solution of 1.5 grams (0.003 mole) of 3-(4-chloro-6-fluoro-2-hydroxy-3-iodophenyl)-1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione, 0.41 gram (0.004 mole) of phenylacetylene, and 0.71 gram (0.007 mole) of triethylamine in 25 mL of DMF was stirred. To this was added 0.09 gram (0.00013 mole) of dichlorobis(triphenylphosphine)pallidium (II) and 0.05 gram (0.00026 mole) of copper (I) iodide. Upon completion of addition, the reaction mixture was heated to 70° C. where it stirred for 2.5 hours. After this time, the reaction mixture was cooled to ambient temperature and then poured into 150 mL of an aqueous 10% ammonium chloride solution. The resulting precipitate was collected by filtration and washed with water. The precipitate was taken up in 120 mL of ethyl acetate. The resulting solution was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a brown solid. The solid was recrystallized using 1:1 chloroform and petroleum ether, yielding 0.31 gram of Compound 280. The mother liquor was concentrated to a residue. The residue was recrystallized using petroleum ether to yield an additional 0.21 gram of Compound 280, m.p. 215-216° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of addition
  2. temperatureAfter this time, the reaction mixture was cooled to ambient temperature
  3. filtrationThe resulting precipitate was collected by filtration
  4. washwashed with water
  5. dry with materialThe resulting solution was dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure to a brown solid
  8. customThe solid was recrystallized

Sources & evidence

ORD record
ord-a485364eb3e8481b9f0a3c7d855917c3
Source dataset
uspto-grants-2000_06
Patent number
US06077812

Reaction notes

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