Diisopropylamine → HCID 58016960, compound

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Reaction Steps

Add 217 ml (0.54 mol) of a 2.5 M n-butyllithium solution in hexane dropwise at −78° C. to a solution of 77 ml (56 g, 0.55 mol) N,N-diisopropylamine in 960 ml 1,2-dimethoxyethane in such a way that the temperature does not exceed −60° C. After stirring for 15 min at this temperature, add a solution of 116 g (0.50 mol) (4-ethylphenyl)[(trimethylsilyl)oxy]acetonitrile [D. S. Dhanoa, J. Med. Chem. 1993, 36 (23), 3738-3742] in 373 ml 1,2-dimethoxyethane dropwise in the space of 30 min. Next, after stirring for 30 min at this temperature, add a solution of 64 g (0.50 mol) 2-fluorobenzaldehyde in 373 ml 1,2-dimethoxyethane dropwise in the space of 20 min. Leave the reaction mixture to warm to room temperature in 4 h. After adding 1900 ml satd. aqueous ammonium chloride solution, extract with ethyl acetate. Wash the organic phase with satd. ammonium chloride solution, dry over sodium sulphate and filter. Concentrate the filtrate by vacuum evaporation. Add 1900 ml dioxan, 1350 ml methanol and 1560 ml 1 M hydrochloric acid to the residue and stir for 16 h at room temperature. After adding 4000 ml satd. aqueous sodium chloride solution, extract with 2000 ml ethyl acetate. Wash the organic phase with 1000 ml water and 1000 ml satd. sodium chloride solution, dry over sodium sulphate and filter. Concentrate the filtrate by vacuum evaporation. Purify the residue by flash chromatography on silica gel (solvent: cyclohexane/ethyl acetate 5:1). Mix the product fraction thus obtained in 80 ml diisopropyl ether and 240 ml petroleum ether, filter, wash with petroleum ether and dry under vacuum. 50 g (85% purity, 33% of theor.) of the title compound is obtained.

Provenance & Evidence