反应详情

Oxalyl choride (5.7 mL) was added dropwise to a solution of 3-(4-chlorophenyl)-2-formylamino-propanoic acid methyl ester (14.5 g, 60 mmol) in CH2Cl2 (400 mL) at room temperature. After stirring for 0.5 hour, ferric chloride (11.7 g) was added and the mixture was stirred for 48 hours. The reaction mixture was diluted with water (500 mL). The organic layer was separated, and the aqueous layer was re-extracted with CH2Cl2 (2×300 mL). The organic layers were combined, washed with brine (200 mL), dried over anhydrous Na2SO4, filtered and concentrated to dryness. The residue was dissolved in MeOH (400 mL), sulfuric acid (20 mL, 98%) was added and the mixture was heated under reflux for 48 hours. After cooled to room temperature, the reaction mixture was diluted with 5% sodium bicarbonate solution (1 L). The organic layer was separated, and the aqueous layer was re-extracted with CH2Cl2 (2×500 mL). The organic layers were combined, washed with brine (500 mL), dried over anhydrous Na2SO4, filtered and concentrated to dryness. The crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/3) and afforded the title compound (3.1 g, 23.3% yield) as a yellow solid. 1H NMR (300 MHz, CDCl3): 9.26 (s, 1H), 8.51 (s, 1H), 8.05 (d, J=1.8 Hz, 1H), 7.93 (d, J=8.7 Hz, 1H), 7.73 (dd, J=1.8 and 8.7 Hz, 1H), 4.06 (s, 3H).

1. stirringthe mixture was stirred for 48 hours
2. customThe organic layer was separated
3. extractionthe aqueous layer was re-extracted with CH2Cl2 (2×300 mL)
4. washwashed with brine (200 mL)
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. dissolutionThe residue was dissolved in MeOH (400 mL)
9. additionsulfuric acid (20 mL, 98%) was added
10. temperaturethe mixture was heated
11. temperatureunder reflux for 48 hours
12. additionthe reaction mixture was diluted with 5% sodium bicarbonate solution (1 L)
13. customThe organic layer was separated
14. extractionthe aqueous layer was re-extracted with CH2Cl2 (2×500 mL)
15. washwashed with brine (500 mL)
16. dry with materialdried over anhydrous Na2SO4
17. filtrationfiltered
18. concentrationconcentrated to dryness
19. customThe crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/3)