4-Methylcyclohexanone → 1-{6-[(Tert-butyldimethylsilanyl)ethynyl]pyridin-3-yl}-4-methylcyclohexanol

Participants

Reaction Steps

9.5 mL (16.19 mmol) of n-BuLi (1.6 M in THF) was slowly added under argon at −70° C. to a solution of 4.50 g (15.19 mmol) of 5-bromo-2-[(tert-butyldimethylsilanyl)ethynyl]pyridine in 50 mL of diethyl ether and 60 mL of THF and after the addition had ended the mixture was stirred for another 2 minutes. 1.86 mL (15.19 mmol) of 4-methylcyclohexanone was added and the mixture was slowly heated to RT. 150 mL of saturated aqueous ammonium chloride solution were added and the aqueous phase was exhaustively extracted with EtOAc. The combined organic extracts were with washed with semisaturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, and evaporated down in vacuo. The residue was purified by chromatography (silica gel, PE/EtOAc 4:1). 2 fractions were isolated. Fraction 1: cis-1-{6-[(tert-butyldimethylsilanyl)ethynyl]pyridin-3-yl}-4-methylcyclohexanol; yield: 1.40 g (28% of theoretical); C20H31NOSi (M=329.552); calc.: molpeak (M+H)+: 330; found: molpeak (M+H)+: 330; Rf value: 0.40 (silica gel, PE/EtOAc 4:1). Fraction 2: trans-1-{6-[(tert-butyldimethylsilanyl)ethynyl]pyridin-3-yl}-4-methylcyclohexanol; yield: 1.00 g (20% of theoretical); C20H31NOSi (M=329.552); calc.: molpeak (M+H)+: 330; found: molpeak (M+H)+: 330; Rf value: 0.30 (silica gel, PE/EtOAc 4:1).

Provenance & Evidence