反应详情

140 g of (8R,9R)-2,3-dimethyl-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one (WO 00/17200, example B1) are suspended in 1100 ml of dichloromethane under argon and with exclusion of moisture. After addition of 70 ml of triethylamine and 2.5 g of 4-dimethyl-aminopyridine, a solution of 62 ml of pivaloyl chloride in 70 ml of dichloromethane is added dropwise such that the temperature of the reaction mixture does not rise above 30° C. (cooling with a water bath). After stirring overnight, the mixture is added to 1 l of ice water and stirred in the cold for a further 10 min. The organic phase is separated off and the aqueous phase is extracted with dichloromethane (2×200 ml). The combined organic phases are washed with water (3×300 ml) until neutral, dried over sodium sulfate and evaporated. 220 g of yellowish oil are obtained, which is crystallized using 600 ml of tert-butyl methyl ether. After stirring in the cold for 2 h, the solid 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. 175 g (97%) of the title compound are obtained as a slightly yellowish solid of m.p. 185-187° C.

1. customdoes not rise above 30° C.
2. temperature(cooling with a water bath)
3. stirringstirred in the cold for a further 10 min
4. customThe organic phase is separated off
5. extractionthe aqueous phase is extracted with dichloromethane (2×200 ml)
6. washThe combined organic phases are washed with water (3×300 ml) until neutral,
7. dry with materialdried over sodium sulfate
8. customevaporated