Sodium Carbonate → (4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((benzyloxy)carbonyl)-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)phenyl)boronic acid

Temperature

90 °C

To a solution of (1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-benzyl 5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(((trifluoromethyl)sulfonyl)oxy)-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 (3.0 g, 4.43 mmol) in THF (100 mL) was added 1,4-benzenediboronic acid (1.469 g, 8.86 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.259 g, 0.222 mmol). The resulting yellow mixture was purged with N2. Then, a solution of sodium carbonate (2.82 g, 26.6 mmol) in H2O (25.00 mL) was added and the reaction mixture was heated to reflux at 90° C. After 6 h, the reaction mixture was cooled to rt, diluted with EtOAc (50 mL) and washed with H2O (50 mL). The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layer was filtered through celite pad, washed with brine, dried over MgSO4, filtered and concentrated to afford a light brown solid. The crude material was absorbed onto silica gel (20 g), loaded onto a silica gel column and eluted with 3:1 hexanes:EtOAc to give (4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((benzyloxy)carbonyl)-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)phenyl)boronic acid (983 mg, 34.2%) as a white solid. 1H NMR (500 MHz, CHLOROFORM-d) δ 8.18-8.14 (m, 2H), 7.43-7.38 (m, 4H), 7.38-7.35 (m, 1H), 7.31-7.29 (m, 1H), 5.37-5.34 (m, 1H), 5.17 (t, J=1.0 Hz, 2H), 4.77 (d, J=1.5 Hz, 1H), 4.64 (s, 1H), 3.08 (td, J=10.8, 4.7 Hz, 1H), 2.35-2.30 (m, 1H), 2.30-2.25 (m, 1H), 2.15 (dd, J=17.1, 6.1 Hz, 1H), 1.98-1.89 (m, 2H), 1.73 (s, 3H), 1.69 (d, J=3.7 Hz, 1H), 1.67-1.64 (m, 1H), 1.56-1.37 (m, 10H), 1.37-1.23 (m, 3H), 1.19 (d, J=13.1 Hz, 1H), 1.07 (dd, J=13.1, 4.3 Hz, 1H), 1.02 (s, 6H), 0.99 (br. s., 3H), 0.99 (br. s., 3H), 0.96-0.93 (m, 1H), 0.87 (s, 3H). 13C NMR (126 MHz, CHLOROFORM-d) δ 175.8, 150.6, 148.41-148.39 (m, 1C), 148.3, 146.8, 136.5, 134.6, 129.7, 128.5, 128.2, 128.1, 123.7, 109.6, 65.7, 56.6, 52.9, 49.6, 49.4, 46.9, 42.4, 41.8, 40.5, 38.4, 37.5, 37.0, 36.3, 33.6, 32.1, 30.6, 29.6, 29.5, 25.7, 21.3, 21.1, 19.8, 19.4, 16.5, 15.6, 14.7.

1. customThe resulting yellow mixture was purged with N2
2. temperaturethe reaction mixture was heated
3. temperaturethe reaction mixture was cooled to rt
4. washwashed with H2O (50 mL)
5. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
6. filtrationThe combined organic layer was filtered through celite pad
7. washwashed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto afford a light brown solid
12. customThe crude material was absorbed onto silica gel (20 g)
13. washeluted with 3:1 hexanes

ORD record

ord-59d44e5285d94653bfc8cfd223f4d0ad

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802661B2