反应详情

温度

120 °C

To a sealable flask containing methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)-2-fluorobenzoate hydrochloride (0.1 g, 0.167 mmol) was added 4-(2-chloroethyl)morpholine hydrochloride (0.093 g, 0.501 mmol), phosphoric acid, potassium salt (0.156 g, 0.735 mmol) and potassium iodide (0.075 g, 0.451 mmol). The mixture was diluted with acetonitrile (3 mL), was flushed with nitrogen, then the vial was sealed and heated to 120° C. After heating the mixture for 16 h, the mixture was cooled to rt. The crude product was adsorbed to silica gel then was purified by flash chromatography using a Thomson 12 g silica gel column and a 0-5% methanol in dichloromethane gradient. The fractions containing the expected product were combined and concentrated under reduced pressure to give methyl 2-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-(2-morpholinoethylamino)-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (77 mg, 0.114 mmol, 68.3% yield) as an off-white foam. LCMS: m/e 675.5 (M+H)+, 1.91 min (method 2).

1. customwas flushed with nitrogen
2. customthe vial was sealed
3. temperatureAfter heating the mixture for 16 h
4. temperaturethe mixture was cooled to rt
5. customthen was purified by flash chromatography
6. additionThe fractions containing the expected product
7. concentrationconcentrated under reduced pressure