反应详情

To a solution of ethyl 4-oxo-1-((4′-(trifluoromethyl)biphenyl-2-yl)methyl)-1,4-dihydro-1,5-naphthyridine-3-carboxylate (37) (11 mg, 0.024 mmol) in dimethyl sulfoxide (1 mL) and methanol (5 mL) was added the solid lithium hydroxide monohydrate (51.0 mg, 1.22 mmol) at room temperature under a nitrogen atmosphere. It gave a clear solution within 30 minutes and this light yellow solution was stirred for 15 h at which time LCMS analysis indicated the absence of starting material. Then, the mixture was diluted with water and the methanol was removed under vacuum. The basic aqueous layer was diluted with water and then neutralized with 1.0N HCl. The resulting acid was extracted with ethyl acetate (2×30 mL) and the combined extracts were washed with brine solution and dried over anhydrous MgSO4. Filtration and concentration gave a brown residue which was dissolved in acetonitrile and water. It was frozen and then lyophilized under high vacuum to obtain 4-oxo-1-((4′-(trifluoromethyl)biphenyl-2-yl)methyl)-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid (38) (4.4 mg, 42.6% yield) as a light yellow solid.

1. customIt gave a clear solution within 30 minutes
2. customthe methanol was removed under vacuum
3. additionThe basic aqueous layer was diluted with water
4. extractionThe resulting acid was extracted with ethyl acetate (2×30 mL)
5. washthe combined extracts were washed with brine solution
6. dry with materialdried over anhydrous MgSO4
7. filtrationFiltration and concentration
8. customgave a brown residue which
9. temperatureIt was frozen