Reacción #172872

Ecuación de reacción

(1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-benzyl 5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(trifluoromethylsulfonyloxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylate

3-fluoro-4-(methoxycarbonyl)phenylboronic acid

sodium carbonate monohydrate

→

title compound

Rendimiento 89.2%

(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-benzyl 9-(3-fluoro-4-(methoxycarbonyl)phenyl)-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]chrysene-3a-carboxylate

Rendimiento 89.2%

Disolventes

1,4-dioxane

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas flushed with N2
2. 2
   Temperaturathe mixture was heated to reflux
3. 3
   TemperaturaAfter 2 h of heating
4. 4
   workup.ADDITIONThe mixture was diluted with water (40 mL)
5. 5
   Extracciónwas extracted with dichloromethane (3×40 mL)
6. 6
   SecadoThe combined organic layers were dried with Na2SO4
7. 7
   OtroThe drying agent was removed by filtration
8. 8
   Concentraciónthe filtrate was concentrated under reduced pressure
9. 9
   workup.DISSOLUTIONThe residue was dissolved in DCM
10. 10
    Filtraciónwas filtered through a pad of celite and silica gel
11. 11
    Lavadowashing with a 25% EtOAc in hexanes solution
12. 12
    ConcentraciónThe filtrate was concentrated under reduced pressure

Procedimiento

A suspension of (1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-benzyl 5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(trifluoromethylsulfonyloxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylate (4.0 g, 5.91 mmol), 3-fluoro-4-(methoxycarbonyl)phenylboronic acid (1.287 g, 6.50 mmol), sodium carbonate monohydrate (2.198 g, 17.73 mmol), and Pd(PPh3)4 (0.205 g, 0.177 mmol) in 1,4-dioxane (24 mL) and water (6 mL) was flushed with N2 and the mixture was heated to reflux. After 2 h of heating, the mixture was cooled to rt. The mixture was diluted with water (40 mL) and was extracted with dichloromethane (3×40 mL). The combined organic layers were dried with Na2SO4. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was dissolved in DCM and was filtered through a pad of celite and silica gel, washing with a 25% EtOAc in hexanes solution. The filtrate was concentrated under reduced pressure to give the title compound (3.59 g, 5.27 mmol, 89% yield) as a dark grey foam. The crude product was used in the next step with no additional purification. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.80 (1H, t, J=7.8 Hz), 7.29-7.42 (5H, m), 6.96 (1H, d, J=7.9 Hz), 6.91 (1H, d, J=11.9 Hz), 5.28-5.33 (1H, m), 5.16 (1H, d, J=12.5 Hz), 5.09 (1H, d, J=12.2 Hz), 4.73 (1H, s), 4.59 (1H, br. s.), 3.92 (3H, s), 3.03 (1H, td, J=10.8, 4.7 Hz), 2.20-2.33 (2H, m), 2.09 (1H, dd, J=17.1, 6.4 Hz), 1.81-1.97 (2H, m), 1.68 (3H, s), 0.96 (3H, s), 0.92 (3H, s), 0.92 (3H, s), 0.91 (3H, s), 0.81 (3H, s), 0.79-1.75 (17H, m).

Fuente