Water → 9-Hydroxy-5-methoxy-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one

9-Benzhydryloxy-7-(2,4-dimethoxy-benzyl)-5-methoxy-pyrrolo [3,4-g]quinoline-6,8-dione 302 (500 mg, 0.89 mmol) was dissolved in tetrahydrofuran (6.0 ml), water (1.2 ml), and isopropanol (2.4 ml) and cooled to 0° C. Lithium borohydride (LiBH4, 96.9 mg, 4.45 mmol) was then added and the reaction mixture was removed from the ice bath and stirred at room temperature for 2 hours. After quenching with acetic acid (0.5 ml), the reaction mixture was diluted with ethyl acetate, washed with twice with water, once with brine, and concentrated in vacuo. The resulting residue was dissolved in dichloromethane (9.2 ml) and triethylsilane (1.8 ml), and cooled to 0° C. After adding trifluoroacetic acid (3.6 ml), the reaction mixture was warmed to room temperature and stirred at room temperature for 1 hour. The mixture was concentrated in vacuo and the resulting residue was redissolved in trifluoroacetic acid (10 ml) and triethylsilane (2 ml). It was then warmed to 75° C. and stirred at 75° C. for 2 hours. The reaction mixture was concentrated in vacuo and azeotroped three times with a (1:1) toluene/tetrahydrofuran solution. The resulting residue was triturated three times with a (3:1) hexane/ether mixture. The remaining solid in the filter funnel and reaction flask was dissolved in methanol, combined, and concentrated in vacuo to afford 9-hydroxy-5-methoxy-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one 303 (240 mg, 113%). 1H NMR (d-DMSO) δ 8.84 (dd, 1H), 8.58 (broad, 1H), 8.50 (dd, 1H), 7.60 (m, 1H), 4.60 (s, 2H), 3.94 (s, 3H). MS: 231.1 (M+1).

1. customthe reaction mixture was removed from the ice bath
2. customAfter quenching with acetic acid (0.5 ml)
3. additionthe reaction mixture was diluted with ethyl acetate
4. washwashed with twice with water
5. concentrationonce with brine, and concentrated in vacuo
6. dissolutionThe resulting residue was dissolved in dichloromethane (9.2 ml)
7. temperaturetriethylsilane (1.8 ml), and cooled to 0° C
8. additionAfter adding trifluoroacetic acid (3.6 ml)
9. temperaturethe reaction mixture was warmed to room temperature
10. stirringstirred at room temperature for 1 hour
11. concentrationThe mixture was concentrated in vacuo
12. dissolutionthe resulting residue was redissolved in trifluoroacetic acid (10 ml)
13. temperatureIt was then warmed to 75° C.
14. stirringstirred at 75° C. for 2 hours
15. concentrationThe reaction mixture was concentrated in vacuo
16. customazeotroped three times with a (1:1) toluene/tetrahydrofuran solution
17. customThe resulting residue was triturated three times with a (3:1) hexane/ether mixture
18. customThe remaining solid in the filter funnel and reaction flask
19. concentrationconcentrated in vacuo

ORD record

ord-95e2e039651a40479b99e0ca0e2eed39

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07253180B2