反应详情

温度

0 °C

114.6 g of powdered 7-(3,4,5-trimethoxy-phenyl)-[1.6]naphthyridine-5-ol is suspended in 900 mL tetrahydrofurane. A solution of 115.9 g of (R)-4-[(S)-1-hydroxyethyl]-1-[(S)-1-(4-methoxyphenyl)-ethyl]-pyrrolidin-2-one and 136 g triphenylphosphine in 1000 mL tetrahydrofurane is added. The suspension is cooled to 0° C. During 40 minutes a solution of 105 mL diisopropylazodicarboxylate [DIAD] in 400 mL tetrahydrofurane is added at 0° C. to 2° C. The suspension is stirred for 3.5 hours at this temperature and then warmed up to 20° C. The solvent is evaporated under reduced pressure. The residue is suspended in 680 mL of tert-butylmethylether. Seeding crystalls of triphenylphosphinoxid are added and the mixture is stirred 16 hours at 20° C. The precipitate is filtered and washed with tert.-butylmethylether. The filtrate is evaporated under reduced pressure. The crude product is dissolved in a mixture of 220 mL of 2-propanol and 1100 mL of isopropyl acetate at 40° C. 48 mL of trimethylchlorosilane are added during 15 minutes. The suspension is stirred for 2 hours at 20° C. The precipitate is filtered and washed with isopropyl acetate and dried at 60° C.

1. temperaturewarmed up to 20° C
2. customThe solvent is evaporated under reduced pressure
3. additionSeeding crystalls of triphenylphosphinoxid are added
4. stirringthe mixture is stirred 16 hours at 20° C
5. filtrationThe precipitate is filtered
6. washwashed with tert.-butylmethylether
7. customThe filtrate is evaporated under reduced pressure
8. dissolutionThe crude product is dissolved in a mixture of 220 mL of 2-propanol and 1100 mL of isopropyl acetate at 40° C
9. addition48 mL of trimethylchlorosilane are added during 15 minutes
10. stirringThe suspension is stirred for 2 hours at 20° C
11. filtrationThe precipitate is filtered
12. washwashed with isopropyl acetate
13. customdried at 60° C.