Tetrabutylammonium Fluoride → Methyl-7-chloro-3-cyclohexyl-1-(2-hydroxyethyl)-2-(4-methoxyphenyl)-1H-indole-6-carboxylate

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Reaction Steps

To a mixture of 131 mgs (1 equivalents, 236 μmol) of Methyl-1-(2-(tert-butyldimethyl silyloxy)ethyl)-7-chloro-3-cyclohexyl-2-(4-methoxy phenyl)-1H-indole-6-carboxylate in 4 mL of THF was added under N2 a 1 M solution of tetrabutylammonium fluoride in THF (2 equivalents, 471 μL). The reaction mixture was stirred for two hours at room temperature. The solution was concentrated en vacuo, washed with water and the product extracted with ethyl acetate. Automated flash chromatography (Biotage Horizon™, gradient elution, 10 to 50% Ethyl Acetate/Hexane) gave 97.0 mgs (93%) of Methyl-7-chloro-3-cyclohexyl-1-(2-hydroxyethyl)-2-(4-methoxyphenyl)-1H-indole-6-carboxylate. The LC/MS data was obtained on a Shimadzu analytical LC/Micromass Platform LC (ESI+) at 220 nm using the following set of conditions: Phenomenex 10 μm C18, 4.6×30 mm column, with a gradient of 0-100% B (B=90% HPLC grade methanol/0.1% trifluoroacetic acid/10% HPLC grade water), (A=90% HPLC grade water/0.1% trifluoroacetic acid/10% HPLC grade methanol), in 2 minutes with a 1 minute hold at a rate of 5 mL/minute. The NMR spectra was recorded at room temperature using a Bruker DRX300 spectrometer. Chemical shifts were reported in ppm relative to the deuterated solvent used. Coupling constants were reported in hertz. Peak multiplicity was reported using the following abbreviations: s (singlet), d (doublet), dd (doublet of doublets), t (triplet), m (multiplet), br (broad). 1H NMR (300 MHz, CDCl3) δ 7.67 (d, J=8.42 Hz, 1H), 7.50 (d, J=8.42 Hz, 1H), 7.25 (d, J=8.78 Hz, 2H), 7.01 (d, J=8.78 Hz, 2H), 4.50 (t, J=6.22 Hz, 2H) 3.94 (s, 3H), 3.89 (s, 3H), 3.76 (t, J=6.22 Hz, 2H), 2.55 (m, 1H), 1.71 (m, 6H) 1.38 (m, 1H) 1.23 (m, 3H). MS m/z 442.15 (M+H), Rf 2.20 min., 96.4% purity.

Provenance & Evidence