1-Butynyltrimethylsilane → tert-Butyl 5-(but-1-yn-1-yl)-7-fluoro-1H-indole-1-carboxylate

HRID 1057136Notes

Reaction equation

HRID 1057136 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[C:19]([Si](C)(C)C)#[C:20][CH2:21][CH3:22].[F:27][C:28]1[CH:29]=[C:30](I)[CH:31]=[C:32]2[C:36]=1[N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH:34]=[CH:33]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:30]1[CH:31]=[C:32]2[C:36](=[C:28]([F:27])[CH:29]=1)[N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH:34]=[CH:33]2)#[C:20][CH2:21][CH3:22]

Participants

7

Reactant 3

HCID 439261-Butynyltrimethylsilane2×HCID 2724141Tetrabutylammonium FluorideHCID 66802356tert-Butyl 7-fluoro-5-iodo-1H-indole-1-carboxylate

Product 1

HCID 69281207tert-Butyl 5-(but-1-yn-1-yl)-7-fluoro-1H-indole-1-carboxylateYield 91%

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 (4.0 mL, 0.5 M THF, 2.00 mmol), but-1-yn-1-yltrimethylsilane (267 mg, 2.11 mmol; Intermediate 39) was added. The solution was stirred at room temperature for a few minutes before transferring into a reaction vessel containing tert-butyl 7-fluoro-5-iodo-1H-indole-1-carboxylate (360 mg, 1.00 mmol), Pd(PPh3)4 (232 mg, 0.20 mmol), and CuI (76 mg, 0.40 mmol). The reaction mixture was stirred at room temperature overnight, diluted with ethyl acetate (100 mL), washed (50 mL water 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 brown oil (260 mg, 91%). 1H NMR (300 MHz, DMSO-d6): δ 7.85 (d, 1H), 7.58 (d, 1H), 7.21 (dd, 1H), 6.83 (dd, 1H), 2.51 (q, 2H), 1.68 (s, 9H), 1.26 (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 water
  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-1c91d1820513409d9a3c5ed68b8407ed
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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