Phthalaldehydic acid → HCID 23122057, compound

2-Formylbenzoic acid (0.15 g, 1.0 mmol) was dissolved in thionyl chloride (1 mL), one drop of pyridine was added thereto, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated, and the residue was dissolved in tetrahydrofuran (5 mL). This solution was added dropwise to a solution of triethylamine (0.19 mL, 1.4 mmol) and hexahydro-1,1-diphenyl-3H-oxazolo[3,4-a]pyrazin-3-one (0.20 g, 0.68 mmol) in tetrahydrofuran (3 mL), and the mixture was stirred at room temperature for 24 hours. The reaction solution was diluted with water and then extracted with ethyl acetate. The organic layer was sequentially washed with 1 N hydrochloric acid, an aqueous saturated sodium hydrogen carbonate solution, water and saturated brine, and dried over magnesium sulfate. The solid was filtered off, and the filtrate was concentrated. The residue was purified with silica gel column chromatography (hexane:ethyl acetate=1:1 to ethyl acetate). The fractions were collected and concentrated. The residue was dissolved in tetrahydrofuran (4 mL). 1,2,3,6-Tetrahydropyridine (0.08 mL, 0.88 mmol) and sodium triacetoxyborohydride (0.13 g, 0.61 mmol) were sequentially added thereto, and the mixture was stirred at room temperature for 25 hours. The reaction solution was diluted with water and then extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over magnesium sulfate. The solid was filtered off, and the filtrate was concentrated. The residue was purified with amino silica gel column chromatography (ethyl acetate:hexane=2:98 to ethyl acetate:hexane=1:1) and silica gel column chromatography (ethyl acetate:hexane=1:1 to ethyl acetate), and then recrystallized from diisopropyl ether to obtain the title compound (68 mg, yield 14%).

1. concentrationThe reaction solution was concentrated
2. dissolutionthe residue was dissolved in tetrahydrofuran (5 mL)
3. stirringthe mixture was stirred at room temperature for 24 hours
4. extractionextracted with ethyl acetate
5. washThe organic layer was sequentially washed with 1 N hydrochloric acid
6. dry with materialan aqueous saturated sodium hydrogen carbonate solution, water and saturated brine, and dried over magnesium sulfate
7. filtrationThe solid was filtered off
8. concentrationthe filtrate was concentrated
9. customThe residue was purified with silica gel column chromatography (hexane:ethyl acetate=1:1 to ethyl acetate)
10. customThe fractions were collected
11. concentrationconcentrated
12. dissolutionThe residue was dissolved in tetrahydrofuran (4 mL)
13. stirringthe mixture was stirred at room temperature for 25 hours
14. extractionextracted with ethyl acetate
15. washThe organic layer was washed with water and saturated brine
16. dry with materialdried over magnesium sulfate
17. filtrationThe solid was filtered off
18. concentrationthe filtrate was concentrated
19. customThe residue was purified with amino silica gel column chromatography (ethyl acetate:hexane=2:98 to ethyl acetate:hexane=1:1) and silica gel column chromatography (ethyl acetate:hexane=1:1 to ethyl acetate)
20. customrecrystallized from diisopropyl ether

ORD record

ord-94fc0fc04b6b4217bd32f7ad1c0aa370

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07795267B2