Trifluoroacetic acid → 4-[(3-Chloro-6-methylphenanthridin-5(6H)-yl)sulfonyl]phenol

A stirred solution of 3-chloro-6-methylphenanthridine (0.40 g, 1.76 mmol) in tetrahydrofuran (7 mL) was treated with freshly crushed sodium borohydride (0.33 g, 8.8 mmol). Trifluoroacetic acid (0.54 mL, 7.0 mmol) was added dropwise at a rate to keep the exothermic reaction and gas evolution under control. After the addition was complete, the heterogeneous reaction mixture was stirred until the temperature returned to 23° C. The mixture was then heated at reflux for 14 hours. The reaction was cooled to room temperature and neutralized with a saturated, aqueous sodium bicarbonate solution (150 mL). The mixture was filtered through a plug of glass wool into a separatory funnel and extracted with diethyl ether (4×50 mL). The combined organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to a light brown paste. The crude 3-chloro-6-methyl-5,6-dihydrophenanthridine was dissolved in pyridine (12 mL), treated with carbonic acid 4-chlorosulfonyl-phenyl ester ethyl ester (0.699 g, 2.64 mmol) and 4-(dimethylamino)pyridine (0.01 g, 0.08 mmol), and stirred at 80° C. for 14 hours. The reaction was cooled to room termperature, treated with a 0.1 N aqueous sodium hydroxide solution (100 mL, 10 mmol), and extracted with dichloromethane (6×50 mL). The combined organic phase was washed with a 2 N hydrochloric acid solution (2×40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to a viscous, brown oil. The viscous oil was purified by filtration through a plug of silica gel, eluting with a mixture of ethyl acetate-hexane (1:4). Concentration of the filtrate in vacuo, followed by trituration with ethyl acetate-hexane afforded the title compound as a homogeneous, white crystalline solid (0.25 g, 37%), m.p. 204° C.;

1. customthe exothermic reaction and gas evolution under control
2. additionAfter the addition
3. customreturned to 23° C
4. temperatureThe mixture was then heated
5. temperatureat reflux for 14 hours
6. filtrationThe mixture was filtered through a plug of glass wool into a separatory funnel
7. extractionextracted with diethyl ether (4×50 mL)
8. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo to a light brown paste
11. dissolutionThe crude 3-chloro-6-methyl-5,6-dihydrophenanthridine was dissolved in pyridine (12 mL)
12. stirringstirred at 80° C. for 14 hours
13. temperatureThe reaction was cooled to room termperature
14. extractionextracted with dichloromethane (6×50 mL)
15. washThe combined organic phase was washed with a 2 N hydrochloric acid solution (2×40 mL)
16. dry with materialdried over anhydrous sodium sulfate
17. filtrationfiltered
18. concentrationconcentrated in vacuo to a viscous, brown oil
19. filtrationThe viscous oil was purified by filtration through a plug of silica gel
20. washeluting with a mixture of ethyl acetate-hexane (1:4)

ORD-Eintrag

ord-d79b1451417a4faa944e07ef6faad645

Quelldatensatz

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06894061B2