Styrene → N-[6-(2-phenylethyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

Participants

Reaction Conditions

Reaction Steps

27.2 cm3 of 9-borabicyclo[3.3.1]nonane are added by syringe to a solution of 0.8 cm3 of styrene in 35 cm3 of dioxane and the mixture is heated at 75° C. for 1 hour. 5.5 cm3 of 5N sodium hydroxide are added to the cooled solution, followed by successive addition of 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide prepared in Example 25, 1.2 g of caesium fluoride, 32.2 mg of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl and 12.3 mg of palladium acetate, and the mixture is heated at reflux for 3 hours. After cooling, 50 cm3 of water and 75 cm3 of ethyl acetate are added; the organic phase is separated out after settling of the phases has taken place, dried over magnesium sulphate, filtered and concentrated under reduced pressure (2 kPa; 40° C.) to give 4.5 g of crude product, which is chromatographed under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with a cyclohexane/ethyl acetate mixture (75/25 by volume). The fractions containing the expected product are combined and then evaporated under reduced pressure (2 kPa; 40° C.) to give 1.4 g of N-[6-(2-phenylethyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

Provenance & Evidence