反应详情

175 g of (8R,9R)-2,3-dimethyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one are dissolved in 2200 ml of toluene under argon and with exclusion of moisture with mechanical stirring. Half the amount of acetyl chloride (130 ml in total) is then added dropwise with ice cooling in the course of 30 min. After removing the ice bath, half the amount of triethylamine (250 ml in total) is then added dropwise at 10° C. in the course of 40 min (warming to 30° C.). After 15 min at this temperature, the procedure is repeated as described with the second half of the reagents indicated. The mixture is then added to 1 l of ice water with stirring. The organic phase is separated off and the aqueous phase is extracted with ethyl acetate (2×200 ml). The combined organic phases are washed with water (3×400 ml), dried over sodium sulfate and evaporated. The yellow-brown residue is crystallized using 300 ml of tert-butyl methyl ether. After stirring in the cold for 1 h, it is filtered off, washed with 200 ml of tert-butyl methyl ether and the filter residue is dried to constant weight in a vacuum drying oven. 186 g (95%) of the title compound are isolated as a yellowish solid of m.p. 168-170° C.

1. customAfter removing the ice bath, half the amount of triethylamine (250 ml in total)
2. additionis then added dropwise at 10° C. in the course of 40 min (warming to 30° C.)
3. additionThe mixture is then added to 1 l of ice water
4. customThe organic phase is separated off
5. extractionthe aqueous phase is extracted with ethyl acetate (2×200 ml)
6. washThe combined organic phases are washed with water (3×400 ml)
7. dry with materialdried over sodium sulfate
8. customevaporated
9. customThe yellow-brown residue is crystallized
10. stirringAfter stirring in the cold for 1 h
11. filtrationit is filtered off
12. washwashed with 200 ml of tert-butyl methyl ether
13. customthe filter residue is dried to constant weight in a vacuum
14. customdrying oven