5-chloro-7-formyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile → (+/-)-5-chloro-7-(1-hydroxyethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

Methylmagnesium bromide (0.334 mL, 1.002 mmol) was added to a −20° C. solution of 5-chloro-7-formyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile (305 mg, 0.911 mmol) in THF (10 mL). The reaction was stirred 1 hour at −20° C., and TLC indicated that reaction was about 50% complete and no longer progressing. More methylmagnesium bromide (0.304 mL, 0.911 mmol) was added and the reaction was stirred an additional 1 hour at −20° C. The reaction was quenched by addition of HCL(1N, 10 mL) and then water (30 mL) was added and the reaction was extracted with ethyl acetate (3×20 mL). The organic layers were washed with brine (20 mL), dried with MgSO4 and evaporated. The residue was purified by chromatography on SiO2 with 20% ethyl acetate/hexanes to provide (±)-5-chloro-7-(1-hydroxyethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile (224 mg, 0.638 mmol, 70.1% yield) as a clear oil. 1H-NMR (CDCl3, 400 MHz) δ 7.66 (d, J=2.0 Hz, 1H), 7.62 (s, 1H), 7.47 (d, J=2.0 Hz, 1H), 5.83 (d, J=11.3 Hz, 1H), 5.56 (pentet, J=6.3 Hz, 1H), 5.48 (d, J=11.3 Hz, 1H), 3.46 (app t, J=8.5 Hz, 2H), 2.27 (d, J=6.1 Hz, 1H), 1.66 (d, J=6.5 Hz, 3H), 0.86 (app t, J=8.3 Hz, 2H), −0.07 (s, 9H). LC/MS (HPLC method 4): tR=3.57 min, 373.16(MNa)+.

Provenance & Evidence