Hydrochloric Acid → 4-[(6-Benzyloxy-7-methoxy-3-nitroquinolin-4-yl)cyanomethyl]benzonitrile

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Reaction Steps

Under a nitrogen atmosphere, 4-cyanophenylacetonitrile (3.86 g, 27.12 mmol) is dissolved in dry tetrahydrofuran (185 ml). Sodium hydride (60% dispersion in paraffin oil, 2.17 g, 54.25 mmol) is subsequently added in portions with ice-bath cooling, and the mixture is stirred for a further 30 min. A suspension of 6-benzyloxy-4-chloro-7-methoxy-3-nitro-quinoline (9.35 g, 27.12 mmol) in N,N-dimethylformamide (50 ml) is then added at room temperature, and the mixture is subsequently stirred for a further 2 h. When the reaction is complete, the mixture is added to 2.5 l of water and neutralised using 1.0 M hydrochloric acid with vigorous stirring. After stirring for 30 min, the suspension is acidified to about pH 2, and, after a further 30 min, the precipitate obtained is filtered off with suction, rinsed with water and dried overnight in a high vacuum. The crude product is subsequently purified over flash silica gel (solvent gradient cyclohexane/0-50% by vol. of ethyl acetate), giving 4-[(6-benzyloxy-7-methoxy-3-nitroquinolin-4-yl)cyanomethyl]benzonitrile (11.31 g, 25.11 mmol) as a solid having a melting point of 147.9° C. MS: 451.1 (M+H+), TLC (HPTLC) (HPTLC): Rf=0.68 (cyclohexane/ethyl acetate 1:1 parts by volume).

Provenance & Evidence