反应详情

温度

75 °C

To a solution of 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 (0.075 g, 0.111 mmol) in 1,4-Dioxane (1 mL) was added NaOH (1M) (0.5 mL, 0.500 mmol). The mixture was heated to 75° C. for 15 h then was cooled to rt. The mixture was acidified with 1N HCl (3 mL) and was concentrated under reduced pressure. The residue was diluted with 15 mL of water and the solids that remained were collected by filtration and were washed with water then with ether. The compound was dissolved in DMF and methanol and was purified by prep HPLC. Fractions containing the expected product were combined and concentrated under reduced pressure to give 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)benzoic acid (30 mg, 0.043 mmol, 38.8% yield) as a white solid. LCMS: m/e 661.5 (M+H)+, 1.67 min (method 2). 1H NMR (500 MHz, Acetic acid d4) ppm 7.96 (1H, t, J=7.9 Hz), 7.09 (1H, dd, J=8.2, 1.2 Hz), 7.03 (1H, d, J=11.6 Hz), 5.42 (1H, d, J=4.6 Hz), 4.86 (1H, s), 4.74 (1H, s), 3.89-3.99 (4H, m), 3.53-3.69 (4H, m), 3.29 (4H, br. s.), 2.81-2.90 (1H, m), 1.77 (3H, s), 1.23 (3H, s), 1.13 (3H, s), 1.08 (3H, s), 1.04 (3H, s), 1.01 (3H, s), 0.85-2.26 (22H, m).

1. temperaturethen was cooled to rt
2. concentrationwas concentrated under reduced pressure
3. additionThe residue was diluted with 15 mL of water
4. filtrationthe solids that remained were collected by filtration
5. washwere washed with water
6. dissolutionThe compound was dissolved in DMF
7. custommethanol and was purified by prep HPLC
8. additionFractions containing the expected product
9. concentrationconcentrated under reduced pressure