Hydrochloric Acid → HCID 10430792, compound

A stirred solution of phenanthridine (7.16 g, 40 mmol) in anhydrous diethyl ether (40 mL) was cooled to −30° C., and treated drop-wise under nitrogen via syringe with a solution of 1.4 M methyllithium in diethyl ether (30 mL, 42 mmol). The yellow solution was warmed to room temperature and stirred for 15 minutes. The mixture was cooled to −78° C., and treated with 5-(chlorosulfonyl)-2-hydroxybenzoic acid (9.47 g, 40 mmol) as a solid in a single aliquot. The reaction mixture was diluted with anhydrous tetrahydrofuran (40 mL), warmed to room temperature, and a solution of N,N-diisopropylethylamine (25.85 g, 200 mmol) in anhydrous dimethylformamide (40 mL) was added. After stirring at room temperature overnight, the reaction mixture was poured into a 1 N hydrochloric acid solution, and extracted with ethyl acetate. The organic phase was washed sequentially with a 1 N aqueous hydrochloric acid solution, water, and a saturated, aqueous, sodium chloride solution. After drying over anhydrous sodium sulfate, the organic phase was filtered and the solvent evaporated in vacuo to yield a crude yellow solid (3.4 g, 21%). The crude solid (1.0 g) was purified by reverse phase preparative chromatography on a Primesphere® 10 C-18 column (25 cm×5 cm), eluting with 56% acetonitrile in water with 0.1% trifluoroacetic acid at a flow rate of 90 mL/min. After evaporation of the acetonitrile solvent, the aqueous phase was extracted with ethyl acetate. The organic phase was washed sequentially with water and a saturated, aqueous, sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent evaporated in vacuo to a colorless solid. Crystallization of the colorless solid from a mixture of diethyl ether-hexane yielded the title compound (0.46 g, 1.16 mmol) as a homogeneous, colorless, crystalline solid, m.p. 225-230° C.;

1. temperatureThe mixture was cooled to −78° C.
2. temperaturewarmed to room temperature
3. stirringAfter stirring at room temperature overnight
4. extractionextracted with ethyl acetate
5. washThe organic phase was washed sequentially with a 1 N aqueous hydrochloric acid solution, water
6. dry with materialAfter drying over anhydrous sodium sulfate
7. filtrationthe organic phase was filtered
8. customthe solvent evaporated in vacuo
9. customto yield a crude yellow solid (3.4 g, 21%)
10. customThe crude solid (1.0 g) was purified by reverse phase preparative chromatography on a Primesphere® 10 C-18 column (25 cm×5 cm)
11. washeluting with 56% acetonitrile in water with 0.1% trifluoroacetic acid at a flow rate of 90 mL/min
12. customAfter evaporation of the acetonitrile solvent
13. extractionthe aqueous phase was extracted with ethyl acetate
14. washThe organic phase was washed sequentially with water
15. dry with materiala saturated, aqueous, sodium chloride solution, dried over anhydrous sodium sulfate
16. customthe solvent evaporated in vacuo to a colorless solid
17. customCrystallization of the colorless solid
18. additionfrom a mixture of diethyl ether-hexane

ORD record

ord-70ef091df9c64cde98cf3cdb6072e8d8

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06894061B2