反应详情

A mixture of 21c and 22c derived from a mixture of 19c and 20c as described above (676 mg, 1.81 mmol), 3-iodobenzylbromide (2.17 mmol, 645 mg), and triethylamine (10 mL) in absolute EtOH (20 mL) was refluxed for 18 h. Volatiles were removed under reduced pressure and the red residue was treated with water. After extraction in dichloromethane (3×30 mL), the combined organic layers were washed with brine, dried over Na2SO4 and concentrated to give a dark red semi-solid residue. Chromatographic purification (silica gel, 50% ethyl acetate-hexanes) afforded 276 mg (30%) of the crude product as a yellow oil. The two regioisomers were separated by HPLC (Silica gel, Hexane/Isopropanol/Triethylamine: 98/2/0.02) and 13d was obtained as a white crystalline solid (166 mg, 18%). Only a trace of the other isomer was recovered. The hydrochloride of 13d was prepared in said methanolic saturated HCl and subsequently recrystallized from 50% i-PrOH-hexanes to provide a white powder; mp 245° C. 1H NMR ((CDCl3) δ1.59-2.06 (m, 8, 2 N--C H2 --C H2), 2.41-2.48 (m, 2, Ar--C H2 --CH2), 2.52-2.62 (m, 2, C H2 --CHOH), 2.75-2.78 (m, 4, Ar--CH2 --C H2 --C H2), 2.83-2.92 (m, 2, C H2 --CH2 --CHOH), 3.01-3.06 (d, 2, N--C H2 --CHN, J=10.0 Hz), 3.38-3.56 (m, 3, Ar--CH2 --N+CH--N), 3.85 (s, 1, C H--OH), 7.02-7.31 (m, 5, arom.), 7.44-7.48 (d, 1, arom., J=7.8 Hz), 7.58-7.62 (d, 1, arom., J=7.9 Hz), 7.68 (s, 1, arom.).

1. temperaturewas refluxed for 18 h
2. customVolatiles were removed under reduced pressure
3. additionthe red residue was treated with water
4. extractionAfter extraction in dichloromethane (3×30 mL)
5. washthe combined organic layers were washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customto give a dark red semi-solid residue
9. customChromatographic purification (silica gel, 50% ethyl acetate-hexanes)
10. customafforded 276 mg (30%) of the crude product as a yellow oil
11. customThe two regioisomers were separated by HPLC (Silica gel, Hexane/Isopropanol/Triethylamine: 98/2/0.02)