1-Butynyltrimethylsilane → 1-(5-(But-1-yn-1-yl)-1H-indol-1-yl)ethanone

HRID 1057127Notes

Reaction equation

HRID 1057127 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[C:19]([Si](C)(C)C)#[C:20][CH2:21][CH3:22].I[C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[N:33]([C:37](=[O:39])[CH3:38])[CH:32]=[CH:31]2>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:19]([C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[N:33]([C:37](=[O:39])[CH3:38])[CH:32]=[CH:31]2)#[C:20][CH2:21][CH3:22]

Participants

7

Reactant 3

HCID 439261-Butynyltrimethylsilane2×HCID 2724141Tetrabutylammonium FluorideHCID 668025481-(5-Iodo-1H-indol-1-yl)ethanone

Product 1

HCID 668020011-(5-(But-1-yn-1-yl)-1H-indol-1-yl)ethanoneYield 96%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a degassed (3× vacuum/nitrogen cycles) solution of TBAF (3.56 mL, 0.5 M THF, 1.78 mmol), but-1-yn-1-yltrimethylsilane (250 mg, 1.98 mmol; Intermediate 39) was added. The solution was stirred at rt for a few minutes before transferring into a reaction vessel containing 1-(5-iodo-1H-indol-1-yl)ethanone (254 mg, 089 mmol), Pd(PPh3)4 (203 mg, 0.18 mmol), and CuI (69 mg, 0.36 mmol). The reaction mixture was stirred at room temperature overnight, diluted with ethyl acetate (50 mL), washed (50 mL saturated NaHCO3 then 50 mL brine), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography to yield the title compound as orange oil (180 mg, 96%). 1H NMR (300 MHz, DMSO-d6): δ 8.26 (d, 1H), 7.89 (d, 1H), 7.64 (d, 1H), 7.32 (dd, 1H), 6.71 (d, 1H), 2.64 (s, 3H), 2.40 (q, 2H), 1.18 (t, 3H).

Workup

  1. additionwas added
  2. custombefore transferring into a reaction vessel
  3. stirringThe reaction mixture was stirred at room temperature overnight
  4. washwashed (50 mL saturated NaHCO3
  5. dry with material50 mL brine), dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-d881fedcf64a4011a46d1248831bc89d
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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