Triethylamine → {5-({[4-(Methyloxy)phenyl]methyl}oxy)-4-[(trimethylsilyl)ethynyl]-2-pyridinyl}methyl acetate

HRID 656965Notes

Reaction equation

HRID 656965 reaction equation
[C:1]([O:4][CH2:5][C:6]1[CH:11]=[C:10](OS(C(F)(F)F)(=O)=O)[C:9]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)=[CH:8][N:7]=1)(=[O:3])[CH3:2].C(N(CC)CC)C.[CH3:37][Si:38]([C:41]#[CH:42])([CH3:40])[CH3:39]>C(#N)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>[C:1]([O:4][CH2:5][C:6]1[CH:11]=[C:10]([C:42]#[C:41][Si:38]([CH3:40])([CH3:39])[CH3:37])[C:9]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)=[CH:8][N:7]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 57423118(5-((4-Methoxybenzyl)oxy)-4-(((trifluoromethyl)sulfonyl)oxy)pyridin-2-yl)methyl acetate

Product 1

HCID 57423117{5-({[4-(Methyloxy)phenyl]methyl}oxy)-4-[(trimethylsilyl)ethynyl]-2-pyridinyl}methyl acetateYield 96%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

Procedure

(5-({[4-(Methoxy)phenyl]methyl}oxy)-4-{[(trifluoromethyl)sulfonyl]oxy}-2-pyridinyl)methyl acetate (for a synthesis, see WO2004058144 Example 60(d)) (10 g, 23 mmol) was dissolved in acetonitrile (400 ml) and triethylamine (65 ml) and copper (I) iodide (0.44 g, 2.3 mmol) were added. The mixture was degassed and placed under a blanket of argon. Trimethylsilylacetylene (10 ml, 69 mmol) and bis(triphenylphosphine)palladium(II) dichloride (0.645 g, 0.9 mmol) were added and the mixture heated to 45° C. for 18 h. The mixture was then allowed to cool and filtered. The filtrate was evaporated to dryness and the residue partitioned between ethyl acetate and water. The organic layer was separated and dried (sodium sulphate). Chromatography on silica gel, eluting with a gradient of 20-75% ethyl acetate in 40-60° C. petroleum ether, gave an oil (8.4 g, 96%).

Workup

  1. customThe mixture was degassed
  2. temperatureto cool
  3. filtrationfiltered
  4. customThe filtrate was evaporated to dryness
  5. customthe residue partitioned between ethyl acetate and water
  6. customThe organic layer was separated
  7. dry with materialdried (sodium sulphate)
  8. washChromatography on silica gel, eluting with a gradient of 20-75% ethyl acetate in 40-60° C. petroleum ether

Sources & evidence

ORD record
ord-db99e3b85a0440b8817fecc383433770
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

Loading…