2-Methylindole → HCID 11258293, compound

Participants

Reaction Conditions

Reaction Steps

To a chilled (−78° C.) solution of 95.0 mg (0.72 mmol) of 2-methylindole in 10 mL of diethyl ether was added 710 μL (1.77 mmol) of a 2.5 M solution of n-BuLi in hexanes. After 5 minutes, 1.16 mL (1.16 mmol) of a 1 M solution of potassium tert-butoxide in THF was added and the mixture was warmed until a yellow precipitate formed. After 20 minutes, the reaction was cooled to −78° C. and 200 mg (0.72 mmol) of 1,1,1-trifluoro-3-(6-fluoro-4-methylchroman-4-yl)propan-2-one (Example 1) in 2 mL of diethyl ether was added. The reaction stirred at −78° C. for 30 minutes and was then warmed to room temperature, quenched with saturated aqueous ammonium chloride and extracted with diethyl ether. The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified on a PLC plate with hexanes-EtOAc (8:2) to afford a mixture of two diastereomers. The diastereomers were separated on a PLC plate (hexanes-CH2Cl2 (1:1)) to give two diastereomer. One was purified again by PLC plate (hexanes-CH2Cl2 (1:1)) to afford 20 mg of the first diastereomer (M+1=408) and the second was triturated with hexanes and the solid collected by filtration to afford 15 mg of the other diastereomer (M+1=408) of the title compound.

Provenance & Evidence