反应详情

温度

0 °C

To a mixture of diisopropylamine (2.42 g, 24.0 mmol) and 8.88 ml (24.0 mmol) butyllithium (2.7M in Heptan) in THF (20 ml) at −70° C. is added a soln. of crotonic acid (1.03 g, 12.0 mmol) in THF (10.0 ml). After stirring at −70° C. and 0° C., a soln. of cyclopropanecarboxylic acid N,O-dimethylhydroxylamide (1.29 g, 10.0 mmol) in THF (10.0 ml) is added. The solution is heated to 48° C. After cooling to −50° C., a solution of glacial acetic acid (5 ml) in THF (10 ml), and 20% aq. NaCl (25 ml) are slowly added. The pH is adjusted to 1.5 with 2M HCl and the mixture is extracted with CH2Cl2 (3×25 ml). Organic phases are washed with 20% aqeous NaCl (2×25 ml) and evaporated to dryness under reduced pressure. The resulting yellow oil is dissolved in toluene (100 ml). 4-Fluoro-2′-aminobenzophenone methansulfonic acid salt (3.23 g, 10.4 mmol) is added and the solution is refluxed in a water separator apparatus for 24 h. Upon cooling, a brown precipitate is formed, which is separated from the mother liquor and purified by chromatography on silica gel (CH2Cl2—MeOH) to afford (E)-3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-acrylic acid. MS (ES): [M−H]− 332.

1. additionis added a soln
2. temperatureThe solution is heated to 48° C
3. temperatureAfter cooling to −50° C.
4. extractionthe mixture is extracted with CH2Cl2 (3×25 ml)
5. washOrganic phases are washed with 20% aqeous NaCl (2×25 ml)
6. customevaporated to dryness under reduced pressure
7. dissolutionThe resulting yellow oil is dissolved in toluene (100 ml)
8. temperatureUpon cooling
9. customa brown precipitate is formed
10. customwhich is separated from the mother liquor
11. custompurified by chromatography on silica gel (CH2Cl2—MeOH)