反应详情

温度

0 °C

Slowly add dropwise ethyl bromoacetate (23 mL; 0.21 mol) over a 3-hour period to a mixture of 2-(2-pyridinyl)-2-(2,4,6-trimethylphenyl)-ethanenitrile (22.3 g; 0.094 mol) and potassium carbonate (78 g; 0.57 mol) suspended in DMSO (100 mL). Stir the mixture for 1 day, pour into an aqueous NH4Cl solution (ca. 1 L), and extract with 3×200 mL of Et2O. Wash the combined extracts with saturated brine, dry over Na2SO4, filter, and concentrate in vacuo. Dissolve the residue in THF (200 mL), cool to 0° C., and add slowly in portions potassium t-butoxide (12 g; 0.11 mol) over a 10-minute period. After 30 minutes at 0° C., dilute the mixture with aqueous NH4Cl and extract with 2×150 mL of 50% Et2O in hexane. Wash the combined extracts with saturated brine, dry over Na2SO4, filter, concentrate in vacuo, and purify by column chromatography on silica gel (eluent: 5 to 10% EtOAc in hexane) to obtain the title compound as an oil: 1H NMR (400 MHz, CDCl3) δ 1.47 (t, 3H), 2.06 (s, 6H), 2.35 (s, 3H), 4.46 (br q, 2H), 6.6 (br t, 1H), 6.75 (d, 1H), 6.9 (br t, 1H), 7.00 (s, 2H), 9.4 (1H).

1. extractionextract with 3×200 mL of Et2O
2. washWash the combined extracts with saturated brine
3. dry with materialdry over Na2SO4
4. filtrationfilter
5. concentrationconcentrate in vacuo
6. dissolutionDissolve the residue in THF (200 mL)
7. waitAfter 30 minutes at 0° C.
8. extractionextract with 2×150 mL of 50% Et2O in hexane
9. washWash the combined extracts with saturated brine
10. dry with materialdry over Na2SO4
11. filtrationfilter
12. concentrationconcentrate in vacuo
13. custompurify by column chromatography on silica gel (eluent: 5 to 10% EtOAc in hexane)