反应详情

4.67 g (123 mmol) lithium aluminium hydride was suspended in 220 ml tetrahydrofuran (THF) and stirred for 20 min. at room temperature. The mixture was cooled to 0° C. and a solution of 15.95 g (61.5 mmol) 6-(4-Fluoro-phenyl)-2-methyl-nicotinic acid ethyl ester (WO 03/068749) in 100 ml added within 15 min. at the same temperature. The mixture was stirred overnight at room temperature (r.t.) and cooled to 0° C. 200 ml of saturated sodium chloride solution were added drop by drop and stirring continued for 60 min. Concentrated HCl was added carefully to adjust the pH to 5. Precipitated salts were filtered off and washed with THF. The combined THF-solutions were evaporated and the residue extracted twice with ethyl acetate. The organic phase was dried (sodium sulphate) and evaporated. The orange resin crystallized after a short time, was stirred with ethyl acetate/n-heptane 1:3, isolated by filtration, washed with tert-butyl-methyl ether and dried. The combined mother liquor from the washings was evaporated and the crystalline precipitate treated as above. The combined yield was 9.25 g (69%) of pale yellow powder.

1. temperatureThe mixture was cooled to 0° C.
2. stirringThe mixture was stirred overnight at room temperature (r.t.)
3. temperaturecooled to 0° C
4. stirringstirring
5. waitcontinued for 60 min
6. filtrationPrecipitated salts were filtered off
7. washwashed with THF
8. customThe combined THF-solutions were evaporated
9. extractionthe residue extracted twice with ethyl acetate
10. dry with materialThe organic phase was dried (sodium sulphate)
11. customevaporated
12. customThe orange resin crystallized after a short time
13. stirringwas stirred with ethyl acetate/n-heptane 1:3
14. customisolated by filtration
15. washwashed with tert-butyl-methyl ether
16. customdried
17. customThe combined mother liquor from the washings was evaporated
18. additionthe crystalline precipitate treated as above