Hydrochloric Acid → HCID 54725308, compound

To a solution of 4-chlorophthalic anhydride (9.13 g, 50 mmol) in tetrahydrofuran (50 ml) was added 28% sodium methoxide-methanol solution (11.6 ml, 60 mmol), and the mixture was stirred at room temperature for 30 min. The reaction mixture was poured into water, and, after making the mixture acidic with 1N hydrochloric acid, extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (100 ml) and oxalyl chloride (5.2 ml, 60 mmol) and N,N-dimethylformamide (3 drops) were added thereto. The mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in N,N-dimethylacetamide (100 ml). To the obtained solution was added ethyl sarcosinate hydrochloride (9.22 g, 60 mmol). The obtained mixture was stirred at room temperature for 2 h. The reaction mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in ethanol (100 ml) and 20% sodium ethoxide ethanol solution (27.2 g, 80 mmol) was added. The mixture was stirred at room temperature for 1 h. The reaction mixture was poured into 1N hydrochloric acid (100 ml) and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography and the component eluted earlier was concentrated to give ethyl 7-chloro-4-hydroxy-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (2.24 g, 20.9%) as crystals.

1. extractionextracted with ethyl acetate
2. washThe extract was washed with brine
3. dry with materialdried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. dissolutionThe residue was dissolved in tetrahydrofuran (100 ml)
6. stirringThe mixture was stirred at room temperature for 30 min
7. concentrationThe reaction mixture was concentrated under reduced pressure
8. dissolutionthe residue was dissolved in N,N-dimethylacetamide (100 ml)
9. stirringThe obtained mixture was stirred at room temperature for 2 h
10. extractionextracted with ethyl acetate
11. washThe extract was washed with brine
12. dry with materialdried over anhydrous magnesium sulfate
13. concentrationconcentrated under reduced pressure
14. dissolutionThe residue was dissolved in ethanol (100 ml)
15. stirringThe mixture was stirred at room temperature for 1 h
16. extractionextracted with ethyl acetate
17. washThe extract was washed with brine
18. dry with materialdried over anhydrous magnesium sulfate
19. concentrationconcentrated under reduced pressure
20. customThe residue was purified by silica gel column chromatography
21. washthe component eluted earlier
22. concentrationwas concentrated

ORD record

ord-cb44278aee8d41f4865f994ca78e93f0

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07034039B2