反应详情

温度

42.5 °C

Under argon and at RT, 476 mg (2.9 mmol, 1.0 eq.) of ethyl 4-aminobenzoate and 41 mg (0.29 mmol, 0.1 eq.) of Oxima and then, dropwise, 452 μl (2.9 mmol, 1.0 eq.) of N,N′-diisopropylcarbodiimide (DIC) were added to a solution of 1.0 g (2.9 mmol) of 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoic acid (racemate) in 10 ml of dimethylformamide. The reaction mixture was stirred at 40-45° C. for 3 h and cooled to RT, methyl tert-butyl ether and water were added and the mixture was stirred vigorously for 10 min, resulting in the formation of a precipitate. The precipitate was filtered off, washed twice with water and methyl tert-butyl ether and dried under reduced pressure (precipitate 1). After phase separation of the combined filtrates, the aqueous phase was extracted once with methyl tert-butyl ether. The combined organic phases were washed once with saturated aqueous sodium chloride solution, dried (sodium sulphate), filtered and concentrated under reduced pressure. The residue was triturated with methyl tert-butyl ether, filtered, washed twice with methyl tert-butyl ether and dried under reduced pressure. This precipitate was stirred in aqueous hydrochloric acid (1N) for 10 min, filtered off, washed twice with water and once with acetonitrile and dried under reduced pressure (precipitate 2). Yield: precipitate 1: 1.12 g (79% of theory), precipitate 2: 127 mg (still contains 1,3-diisopropylurea according to 1H NMR)

1. temperaturecooled to RT
2. stirringthe mixture was stirred vigorously for 10 min
3. customresulting in the formation of a precipitate
4. filtrationThe precipitate was filtered off
5. washwashed twice with water and methyl tert-butyl ether
6. dry with materialdried under reduced pressure (precipitate 1)
7. customAfter phase separation of the combined filtrates
8. extractionthe aqueous phase was extracted once with methyl tert-butyl ether
9. washThe combined organic phases were washed once with saturated aqueous sodium chloride solution
10. dry with materialdried (sodium sulphate)
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe residue was triturated with methyl tert-butyl ether
14. filtrationfiltered
15. washwashed twice with methyl tert-butyl ether
16. customdried under reduced pressure
17. stirringThis precipitate was stirred in aqueous hydrochloric acid (1N) for 10 min
18. filtrationfiltered off
19. washwashed twice with water and once with acetonitrile
20. dry with materialdried under reduced pressure (precipitate 2)