反应详情

温度

-78 °C

To a solution of 5.4 g (25.5 mmol) of 5-ethyl-2-thiophenecarboxylic acid, N-t-butyl amide, from step 3b above, in 80 mL of THF cooled to -78° C. was added 20.4 mL (51.1 mmol) of n-butyllithium (2.5M in hexane). The solution was then stirred at 0° for 40 min, then re-cooled to -78° C., and a solution of 6.0 g of 1,2-dihydro-6,7-dimethoxy-3-nitronaphthalene, from Example 1 b above, in 100 mL of THF cooled to -78° C. was added via cannula. The solution was stirred at -78° C. for 1 hour and at 0° C. for 1 hour. The reaction was quenched with saturated NH4Cl, diluted with water, and extracted with methylene chloride. The extract was washed with brine, dried and concentrated. The residue was dissolved in 30 mL of acetonitrile, 1 mL of triethylamine was added, and the reaction was stirred for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography, eluting with 6:1 hexane:ethyl acetate to afford 5.7 g of the title product. MS 447 (M+H)+, 464 (M+NH4)+. NMR (CDCl3), δ:6.48 (s, 1H), 6.37 (s, 1H), 6.30 (s, 1H), 5.70 (bs, 1H, 5.47 (d, 1H, J=8 Hz), 5.05 (m, 1H), 3.85 (s, 3H) 3.69 (s, 3H), 3.2-2.88 (m, 2H), 2.72 (q, 2H, J=7 Hz), 2.5-2.35 (m, 2H), 1.42 (s, 3H), 1.23 (t, 3H, J=7 Hz).

1. additionwas added via cannula
2. stirringThe solution was stirred at -78° C. for 1 hour and at 0° C. for 1 hour
3. customThe reaction was quenched with saturated NH4Cl
4. additiondiluted with water
5. extractionextracted with methylene chloride
6. washThe extract was washed with brine
7. customdried
8. concentrationconcentrated
9. dissolutionThe residue was dissolved in 30 mL of acetonitrile
10. addition1 mL of triethylamine was added
11. stirringthe reaction was stirred for 16 hours
12. customThe solvent was evaporated
13. customthe residue was purified by flash chromatography
14. washeluting with 6:1 hexane