反应详情

温度

100 °C

To a stirred solution of 1,4,8,11-tetra(p-toluenesulfonyl)-1,4,8,11-tetraazaundecane prepared in Example 16A (80.7 g, 0.104 mole) in anhydrous DMF (1 l) was added sodium hydride (6.24 g-80% in mineral oil, 0.208 mole) in portions under a dry nitrogen blanket. The resulting mixture was stirred for 30 minutes under a dry argon atmosphere. The solution was then heated to 100° C. and a solution of N-methylbis(2-chloroethyl)amine freshly prepared as in Example 15A (16.2 g, 0.104 mole) in anhydrous DMF (200 ml) was added dropwise over a 45 minute period, maintaining the temperature at 100° C. After stirring, an additional 45 minutes at 100° C., the solution was concentrated in vacuo to a volume of 900 ml. H2O (1200 ml) was added at room temperature to crystallize the product. The solid was dried in vacuo over P2O5 to give 83.2 g (93% yield) of the crude product as a brown solid. A portion (50 g) of the crude product was purified by flash chromatography (silica gel, CHCl3 --95:5 (v/v) --CHCl3 --MeOH gradient) to give 16.8 g (34% yield) of the product as a light yellow solid. An analytical sample was recrystallized from CH2Cl2 -hexane: mp 183°-5° C.; Rf =0.60, silica gel--95:5 (v/v) CHCl3 -MeOH; 1H NMR (CDCl3) δ 1.91 (quint, J=6.0 Hz, 2 H), 2.19 (s, 3 H), 2.44 (s, 12 H), 2.52 (t, J=6.2 Hz, 4 H), 3.18 (m, 12 H), 3.31 (m, 4 H), 7.33 (m, 8 H), 7.68 (m, 8 H).

1. additionwas added dropwise over a 45 minute period
2. temperaturemaintaining the temperature at 100° C
3. stirringAfter stirring, an additional 45 minutes at 100° C.
4. concentrationthe solution was concentrated in vacuo to a volume of 900 ml
5. additionH2O (1200 ml) was added at room temperature
6. customto crystallize the product
7. dry with materialThe solid was dried in vacuo over P2O5
8. customto give 83.2 g (93% yield) of the crude product as a brown solid
9. customA portion (50 g) of the crude product was purified by flash chromatography (silica gel, CHCl3 --95:5 (v/v) --CHCl3 --MeOH gradient)