反应详情

温度

-40 °C

To a solution of (1,4-dioxa-spiro[4.5]dec-8-yl)-acetic acid ethyl ester (3.6 g, 15.77 mmol) in THF (50 mL) cooled to −78° C. was added LiHMDS (1M in THF, 18.1 mL) under argon. The resulting solution was stirred for 1 h at −40° C., then recooled to −78° C. 6-methoxy-[1,5]naphthyridine-4-carbaldehyde (3.56 g, 18.92 mmol; prepared according to WO 2006/032466) was added portionwise and stirring was continued for 30 min at −78° C. The reaction mixture was quenched by the addition of aq. NH4Cl. The two layers were separated and the aq. layer was extracted with EA. The combined org. layers were washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was chromatographed (Hept-EA 1-2→EA) to afford a diastereoisomeric 1:1 mixture of the title compound as a pale yellow oil (4.44 g, 68% yield).

1. customrecooled to −78° C
2. stirringstirring
3. waitwas continued for 30 min at −78° C
4. customThe reaction mixture was quenched by the addition of aq. NH4Cl
5. customThe two layers were separated
6. extractionthe aq. layer was extracted with EA
7. washlayers were washed with brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated to dryness
11. customThe residue was chromatographed (Hept-EA 1-2→EA)
12. customto afford