Diethyl Carbonate → ethyl 6-fluoro-1-(triisopropylsilyl)-1H-indole-5-carboxylate

HRID 336823Notes

Reaction equation

[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])=[CH:4][CH:3]=1.C([Li])(CC)C.[C:26](=O)([O:30]CC)[O:27][CH2:28][CH3:29].[Cl-].[NH4+]>O1CCCC1>[C:26]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[F:1])[N:8]([Si:11]([CH:15]([CH3:17])[CH3:16])([CH:18]([CH3:20])[CH3:19])[CH:12]([CH3:13])[CH3:14])[CH:7]=[CH:6]2)([O:27][CH2:28][CH3:29])=[O:30]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 760 mg (2.61 mmol) of 6-fluoro-1-triisopropylsilylindole dissolved in 6 ml of anhydrous tetrahydrofuran are added dropwise at −78° C. under argon 2.01 ml of a sec-butyllithium solution (1.3M in cyclohexane, 2.01 mmol). The reaction mixture is stirred for 2 h at −78° C. then 500 μL (3.15 mmol) of diethyl carbonate are added dropwise at −78° C. to the reaction mixture. This mixture is stirred for 5 h with a gentle temperature rise then an ammonium chloride saturated aqueous solution is added. The product is extracted several times with ethyl acetate. The organic phases are combined, dried over magnesium sulfate, and concentrated. The residue is purified by chromatography on silica (cyclohexane/ethyl acetate eluent: 97:3) to yield 445 mg (46%) of 5-carboethoxy-6-fluoro-1-triisopropylsilylindole in the form of a colourless oil.

Workup

stirringThis mixture is stirred for 5 h with a gentle temperature rise
extractionThe product is extracted several times with ethyl acetate
dry with materialdried over magnesium sulfate
concentrationconcentrated
customThe residue is purified by chromatography on silica (cyclohexane/ethyl acetate eluent: 97:3)

Sources & evidence

ORD record: ord-d65a3426479a4ba0809f4a699a88bc45
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889711B2

Reaction notes

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