反应详情

温度

20 °C

(S)-Ethyl 6-bromo-2-ethyl-8-methoxy-4-methyl-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-7-carboxylate (0.70 mol) was dissolved in THF (4500 ml) at 20° C. Molecular sieves (4 Å; 250 g) were added. The mixture was stirred for 30 min at 20° C., and was then cooled to −78° C. A solution of n-Butyllithium (2.5 M; 0.77 mol) was added dropwise below −65° C. The mixture was stirred for 1 h at −78° C. Diethyl oxalate (1.6 mol) in THF (600 ml) was added dropwise below −65° C. and then it was stirred for 3 h. The mixture was poured into a solution of aqueous H2SO4 (4200 ml, 2 M) and THF (3500 ml). The organic layer was separated and the aqueous layer was re-extracted with ethyl acetate (3×2000 ml). The combined organic layers were collected and evaporated. The residue was purified by column chromatography over silica gel (eluent: petroleum ether/ethyl acetate from 100:0 to 1:1). The pure fractions were collected and the organic solvent was evaporated. Yield: 170 g (67% yield).

1. additionMolecular sieves (4 Å; 250 g) were added
2. temperaturewas then cooled to −78° C
3. stirringThe mixture was stirred for 1 h at −78° C
4. stirringit was stirred for 3 h
5. customThe organic layer was separated
6. extractionthe aqueous layer was re-extracted with ethyl acetate (3×2000 ml)
7. customThe combined organic layers were collected
8. customevaporated
9. customThe residue was purified by column chromatography over silica gel (eluent: petroleum ether/ethyl acetate from 100:0 to 1:1)
10. customThe pure fractions were collected
11. customthe organic solvent was evaporated