反应详情

A 50 mL round-bottom flask equipped with rubber septum and nitrogen inlet needle was charged with rac-(2′R,4aS,12bR)-12b-ethyl-9-(2-methylpyridin-4-yl)-1,2,4,4a,5,6,9,12b-octahydrospiro[benzo[4,5]oxepino[3,2-f]indazole-3,2′-oxirane] (93, R1=2-Methylpyridin-4-yl, R2=Ethyl) (0.200 g, 0.513 mmol) and NaOMe (0.5 M in MeOH) (5.1 mL, 2.57 mmol). The resulting solution was allowed to stir at rt for about 16 h, after which the reaction solution was concentrated under reduced pressure. The residue was partitioned between a mixture of water (20 mL) with sat. aq. NH4Cl (5 mL) and EtOAc (25 mL). After separating the layers, the aqueous phase was extracted with EtOAc (2×10 mL). The combined organic phases were washed with brine (25 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The sample was purified on silica gel (4 g, EtOAc). Collection and concentration of the appropriate fractions gave rac-(3R,4aS,12bR)-12b-ethyl-3-(methoxymethyl)-9-(2-methylpyridin-4-yl)-2,3,4,4a,5,6,9,12b-octahydro-1H-benzo[4,5]oxepino[3,2-f]indazol-3-ol (94, R1=2-methylpyridin-4-yl, R2=Ethyl, R3=Methoxymethyl) (198 mg, 92%). LC/MS, method 2, Rt=2.04 min, MS m/z 422 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J=5.8 Hz, 1H), 8.20 (s, 1H), 7.86-7.72 (m, 2H), 7.64 (s, 1H), 7.53 (s, 1H), 4.39-4.30 (m, 1H), 3.81-3.71 (m, 1H), 3.33 (s, 3H), 3.19-3.02 (m, 2H), 2.87-2.70 (m, 3H), 2.53-2.45 (m, 1H), 2.38-2.20 (m, 3H), 1.96-1.85 (m, 1H), 1.82-1.65 (m, 2H), 1.63-1.36 (m, 4H), 1.34-1.22 (m, 1H), 0.60 (t, J=7.4 Hz, 3H).

1. customA 50 mL round-bottom flask equipped with rubber septum and nitrogen inlet needle
2. concentrationafter which the reaction solution was concentrated under reduced pressure
3. customThe residue was partitioned between a mixture of water (20 mL) with sat. aq. NH4Cl (5 mL) and EtOAc (25 mL)
4. customAfter separating the layers
5. extractionthe aqueous phase was extracted with EtOAc (2×10 mL)
6. washThe combined organic phases were washed with brine (25 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe sample was purified on silica gel (4 g, EtOAc)
11. customCollection and concentration of the appropriate fractions