Toluene → 1-cyclopentyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile

HRID 1028003Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:16]#[N:17])=[CH:7][N:8]2[CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:4][C:3]=1[F:18].[CH3:19][Zn]C.C1(C)C=CC=CC=1>O1CCOCC1>[CH:11]1([N:8]2[C:9]3[C:5](=[CH:4][C:3]([F:18])=[C:2]([CH3:19])[CH:10]=3)[C:6]([C:16]#[N:17])=[CH:7]2)[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

Conditions

Temperature: 90 °C

Procedure

Into a solution of 6-bromo-1-cyclopentyl-5-fluoro-1H-indole-3-carbonitrile (6.6 g, 21.5 mmol) and PdCl2dppf (0.31 g, 0.43 mmol) in dioxane (45 mL) was added a solution of dimethylzinc in toluene (1.2 M, 35.8 mL, 43 mmol). The atmosphere was replaced with nitrogen. The mixture was stirred at 90° C. for 90 min and then cooled to room temperature. The reaction was quenched by careful addition of methanol. Ethyl acetate (200 mL) was added and the mixture washed with aq. 2 N HCl, water and brine, dried over Na2SO4 and concentrated. The residue was purified on silica gel eluting with a gradient of 5 to 35% ethyl acetate in hexane to provide 1-cyclopentyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile (4.4 g, 85%)

Workup

temperaturecooled to room temperature
customThe reaction was quenched by careful addition of methanol
additionEthyl acetate (200 mL) was added
washthe mixture washed with aq. 2 N HCl, water and brine
dry with materialdried over Na2SO4
concentrationconcentrated
customThe residue was purified on silica gel eluting with a gradient of 5 to 35% ethyl acetate in hexane

Sources & evidence

ORD record: ord-6e92594c28c1456eaf61c3c528f6ae8b
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08735414B2

Reaction notes

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