反应详情

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).

1. temperaturecooling
2. additionis then added at room temperature
3. stirringthe mixture is subsequently stirred for a further 2 h
4. stirringAfter stirring for 30 min
5. waitafter a further 30 min
6. customthe precipitate obtained
7. filtrationis filtered off with suction
8. washrinsed with water
9. customdried overnight in a high vacuum
10. customThe crude product is subsequently purified over flash silica gel (solvent gradient cyclohexane/0-50% by vol. of ethyl acetate)