Trimethylsilylacetylene → HCID 12135110, compound

HRID 1835659Notes

Reaction equation

HRID 1835659 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:22]([F:23])=[C:21]([F:24])[CH:20]=[CH:19][C:11]=1[C:12]([NH:14][O:15][CH2:16][CH2:17][OH:18])=[O:13].[CH3:25][Si:26]([C:29]#[CH:30])([CH3:28])[CH3:27]>C(N(CC)CC)C.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>[Cl:1][C:2]1[CH:7]=[C:6]([C:30]#[C:29][Si:26]([CH3:28])([CH3:27])[CH3:25])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:22]([F:23])=[C:21]([F:24])[CH:20]=[CH:19][C:11]=1[C:12]([NH:14][O:15][CH2:16][CH2:17][OH:18])=[O:13]

Participants

5

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 10162188HCID 10162188, compound2×

Product 1

HCID 12135110HCID 12135110, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

The product of Example 6, Step C, 2-(2-chloro-4-iodo-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (3.25 g, 6.93 mmol) and (trimethylsilyl)acetylene (1.10 mL, 7.78 mmol) were combined in triethylamine (17 mL). Dichlorobis(triphenylphosphine)-palladium(II) (0.120 g, 0.017 mol) and cuprous iodide (0.033 g, 0.17 mmol) were added and the resultant solution was stirred at ambient temperature for 22 h. The reaction mixture was adsorbed onto Celite® for 20 min and was filtered, washing with ethyl acetate. The filtrate was concentrated to a thick oil, further diluted with ethyl acetate (100 mL) and washed with aqueous citric acid (2 M, 2×25 mL), water, and brine. The organic layer was then dried over magnesium sulfate and concentrated in vacuo to afford a tan-colored solid. Recrystallization form heptane-ethyl acetate afforded 2-(2-chloro-4-trimethylsilanylethynyl-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (2.34 g, 76% yield) as a grey-colored solid: 1H NMR (400 MHz, DMSO-d6) δ 11.96 (s, 1 H), 8.95 (s, 1 H), 7.53 (d, J=1.7 Hz, 1 H), 7.47 (m, 1 H), 7.32 (m, 1 H), 7.27 (dd, J=8.4, 1.8 Hz, 1 H), 6.72 (dd, J=8.0, 6.6 Hz, 1 H), 4.73 (t, J=5.5 Hz, 1 H), 3.87 (apparent t, J=4.7 Hz, 2 H), 3.57 (m, 2 H), 0.21 (s, 9 H); MS (APCI+)=439.1; MS (APCI−)=437.1.

Workup

  1. filtrationwas filtered
  2. washwashing with ethyl acetate
  3. concentrationThe filtrate was concentrated to a thick oil
  4. additionfurther diluted with ethyl acetate (100 mL)
  5. washwashed with aqueous citric acid (2 M, 2×25 mL), water, and brine
  6. dry with materialThe organic layer was then dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customto afford a tan-colored solid
  9. customRecrystallization
  10. customform heptane-ethyl acetate

Sources & evidence

ORD record
ord-0f859a2fc97a424199b55589bc5f9662
Source dataset
uspto-grants-2004_08
Patent number
US06770778B2

Reaction notes

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