反应详情

A solution of 4-chloropropiophenone (16.9 g, 100 mmol) in diethylether (20 ml) was added to a solution of LiN(TMS)2 (1 M solution in THF, 100 ml, 100 mmol) in diethylether (400 ml) at −78° C. The reaction mixture was stirred at −78 C for 0.75 hour, then diethyl oxalate (15 ml, 110 mmol) was added dropwise. The reaction mixture was slowly allowed to warm to room temperature and stir for 17 hours. The diethyl ether was removed under vacuum and the residue was diluted with diethyl ether. A light yellow solid precipitated out of solution and was collected by filtration (9.9 g, 36%). This solid, which was used without further purification, was dissolved in isopropyl alcohol (200 ml), and 2-chlorophenylhydrazine (5.9 g, 36.1 mmol) and conc. H2SO4 (0.4 ml) was added. The reaction mixture was heated under reflux for 17 hours. After cooling to room temperature, NaHCO3 (1 g) was added. The reaction mixture was concentrated under vacuum. The residue was diluted with EtOAc and the organic solution was washed with sat'd aq NaHCO3 and sat'd aq NaCl, dried, filtered, and concentrated in vacuo. The residue was triturated with cyclohexane to give I-4a as an off-white solid (9.5 g, 25%): +APCI MS (M+1) 375.0.

1. stirringstir for 17 hours
2. customThe diethyl ether was removed under vacuum
3. additionthe residue was diluted with diethyl ether
4. customA light yellow solid precipitated out of solution
5. filtrationwas collected by filtration (9.9 g, 36%)
6. customThis solid, which was used without further purification
7. dissolutionwas dissolved in isopropyl alcohol (200 ml)
8. temperatureThe reaction mixture was heated
9. temperatureunder reflux for 17 hours
10. temperatureAfter cooling to room temperature
11. concentrationThe reaction mixture was concentrated under vacuum
12. additionThe residue was diluted with EtOAc
13. washthe organic solution was washed with sat'd aq NaHCO3
14. customdried
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customThe residue was triturated with cyclohexane