反应详情

温度

60 °C

Freshly prepared sodium ethoxide (1 M solution in EtOH, 3.00 mL, 3.00 mmol) was added to a mixture of (4aR,12bR)-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3 (2H)-one; compound with (4aS,12bS)-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3 (2H)-one (4aR,12bR)-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3 (2H)-one (9, R1=4-Fluorophenyl, R2=Ethyl) (0.750 g, 1.99 mmol), THF (6.50 mL) and EtOH (13.0 mL) under a nitrogen atmosphere. Benzaldehyde (0.220 mL, 2.17 mmol) was added. After about 3 h, sodium ethoxide (1 M solution in EtOH, 3.00 mL, 3.00 mmol) was added. After about 15 h, the mixture was warmed to about 60° C. After about 30 min, the mixture was allowed to cool to rt. AcOH (0.500 mL) was added. The volatiles were removed under reduced pressure. Water (25 mL) and DCM (50 mL) were added. The layers were separated and the organics were washed with sat. aq. NaCl (25 mL) then dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel (80 g) using a gradient of 0-25% EtOAc in heptane. The fractions containing product were combined and concentrated under reduced pressure to afford (4aR,12bR,E)-2-benzylidene-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3(2H)-one; compound with (4aS,12bS,E)-2-benzylidene-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3(2H)-one (68, R1=4-Fluorophenyl, R2=Ethyl) (0.545 g, 59% yield) as an ivory solid. LC/MS, method 3, Rt=3.05 min, MS m/z 465 (M+H)+. 1H NMR (400 MHz, DMSO) δ 7.98 (s, 1H), 7.81-7.74 (m, 2H), 7.67-7.62 (m, 2H), 7.62-7.53 (m, 4H), 7.53-7.45 (m, 2H), 7.44-7.35 (m, 2H), 3.37-3.32 (m, 2H), 3.28-3.17 (m, 1H), 2.98-2.87 (m, 1H), 2.62-2.43 (m, 2H), 2.38-2.25 (m, 1H), 2.16-1.89 (m, 3H), 1.75-1.64 (m, 1H), 1.51-1.23 (m, 2H), 0.19 (t, J=7.2 Hz, 3H).

1. waitAfter about 15 h
2. waitAfter about 30 min
3. temperatureto cool to rt
4. customThe volatiles were removed under reduced pressure
5. additionWater (25 mL) and DCM (50 mL) were added
6. customThe layers were separated
7. washthe organics were washed with sat. aq. NaCl (25 mL)
8. dry with materialthen dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified on silica gel (80 g)
12. additionThe fractions containing product
13. concentrationconcentrated under reduced pressure