tert-Butyl methyl ether → HCID 22639913, compound

HRID 2415028Notes

Reaction equation

HRID 2415028 reaction equation
I[C:2]1[C:3]([O:13][CH3:14])=[N:4][C:5]([CH3:12])=[N:6][C:7]=1[C:8]([F:11])([F:10])[F:9].[CH3:15][Si:16]([C:19]#[CH:20])([CH3:18])[CH3:17].C(OC)(C)(C)C>CN(C=O)C.C(N(CC)C(C)C)(C)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:14][O:13][C:3]1[C:2]([C:20]#[C:19][Si:16]([CH3:18])([CH3:17])[CH3:15])=[C:7]([C:8]([F:11])([F:10])[F:9])[N:6]=[C:5]([CH3:12])[N:4]=1

Participants

8

Reactant 3

HCID 15413tert-Butyl methyl etherHCID 66111TrimethylsilylacetyleneHCID 12151205HCID 12151205, compound

Product 1

HCID 22639913HCID 22639913, compoundYield 116.9%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
50 °C

Procedure

5-Iodo-4-methoxy-2-methyl-6-trifluoromethylpyrimidine (5.0 g) was dissolved in DMF (50 ml) and N,N-diisopropylethylamine (6.5 g), copper(I) iodide (0.3 g), dichlorobis(triphenylphosphine)palladium(II) (1.12 g) and trimethylsilylacetylene (15.4 g) was added at room temperature with stirring. The mixture was heated (50° C.) in nitrogen atmosphere for 7 hr and cool to room tempeature. The reaction mixture was added methyl tert-butyl ether (MTBE) (200 ml). The insoluble matter was removed by filtration through Celite and the filtrate was washed with water and brine, respectively. The MTBE solution was dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give crude 4-methoxy-2-methyl-6-trifluoromethyl-5-trimethylsilylethynylpyrimidine (5.3 g) as pale yellow oil. This crude 4-methoxy-2-methyl-6-trifluoromethyl-5-trimethylsilylethynylpyrimidine (5.2 g) was dissolved in THF (100 ml) and tetrabutylammonium fluoride (1M THF solution, 18 ml) was added under ice cooling with stirring. After stirring 30 min at this temperature, the reaction mixture was added water in one portion under ice cooling and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, respectively and dried over magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane ethyl acetate) to give 5-ethynyl-4-methoxy-2-methyl-6-trifluoromethylpyrimidine (1.92 g) as colorless crystalline solid, mp 77° C.

Workup

  1. temperaturecool to room tempeature
  2. customThe insoluble matter was removed by filtration through Celite
  3. washthe filtrate was washed with water and brine
  4. dry with materialThe MTBE solution was dried over magnesium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-49eac1b35b624b2ab6dad4e82ff06eef
Source dataset
uspto-grants-2004_11
Patent number
US06818631B1

Reaction notes

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