Cyclohexanol → 2-Fluoro-4-[4-(methoxymethylidene)cyclohexyl]benzonitrile

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Reaction Steps

1.8 g of solid potassium t.-butylate are added at -15° to a suspension of 5.3 g of triphenylmethoxymethylphosphonium chloride in 100 ml of diisopropyl ether, and the mixture is stirred for a further 30 minutes. A solution of 2.3 g of 4-(4-cyano-3-fluorophenyl)-cyclohexanone [obtainable by reacting 4-bromo-2-fluorobenzonitrile and cyclohexane-1,4-dione monoethylene ketal with butyllithium in ether at -100° by the method of W. E. Porham and L. D. Jones, J. Org. Chem. 41, 1187, 2704 (1976), subsequently eliminating water from the resulting cyclohexanol, hydrogenating the double bond and splitting off the ethylene ketal protective group] in 30 ml of THF is then added dropwise to the suspension, and the reaction mixture is stirred for a further 3 hours at room temperature, then poured into 300 ml of petroleum ether and filtered. Working up the filtrate in the customary manner gives 4-[4-(methoxymethylene)cyclohexyl]-2-fluorobenzonitrile as a colourless oil. A mixture of 1.0 g of this oil, 20 ml of THF and 5 ml of 2N hydrochloric acid is boiled for 30 minutes and then worked up in the customary manner. Trans-4-(4-cyano-3-fluorophenyl)-cyclohexanecarbaldehyde is obtained after crystallisation.

Provenance & Evidence