Hydrochloric Acid → HCID 54725303, compound

A solution of 5-benzyloxy-2-(ethoxycarbonyl)benzoic acid (21.86 g, 120 mmol), ethyl 2-(neopentylamino)acetate (20.79 g, 120 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (28.76 g, 150 mmol) and 1-hydroxybenzotriazole (22.97 g, 150 mmol) in N,N-dimethylformamide (200 ml) was stirred at room temperature for 3 h. The reaction mixture was poured into water 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 N,N-dimethylformamide (300 ml), and potassium carbonate (33.17 g, 240 mmol) and benzyl bromide (35.7 ml, 300 mmol) were added. The mixture was stirred at room temperature for 12 h. The reaction mixture was poured into water 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 (50 ml) and 20% sodium ethoxide ethanol solution (34.04 g, 100 mmol) was added. The mixture was stirred at room temperature for 1 h. The reaction mixture was poured into 1N hydrochloric acid (150 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-benzyloxy-4-hydroxy-2-neopentyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate as an oil. To a solution of the obtained ethyl 7-benzyloxy-4-hydroxy-2-neopentyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (3.26 g, 8 mmol), 1-butanol (1.1 ml, 12 mmol) and tributylphosphine (4.0 ml, 16 mmol) in tetrahydrofuran (30 ml) was added 1,1′-(azodicarbonyl)dipiperidine (4.04 g, 16 mmol) and the mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography to give ethyl 7-benzyloxy-4-butoxy-2-neopentyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (3.61 g, 97.0%) as an oil.

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 N,N-dimethylformamide (300 ml)
6. extractionextracted with ethyl acetate
7. washThe extract was washed with brine
8. dry with materialdried over anhydrous magnesium sulfate
9. concentrationconcentrated under reduced pressure
10. dissolutionThe residue was dissolved in ethanol (50 ml)
11. stirringThe mixture was stirred at room temperature for 1 h
12. extractionextracted with ethyl acetate
13. washThe extract was washed with brine
14. dry with materialdried over anhydrous magnesium sulfate
15. concentrationconcentrated under reduced pressure
16. customThe residue was purified by silica gel column chromatography
17. washthe component eluted earlier
18. concentrationwas concentrated

ORD record

ord-a60faaea9e11492ba1aef43a5eff7599

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07034039B2