反应详情

温度

85 °C

In a 1 L 3 neck RBF equipped with magnetic stir bar, condenser, thermocouple, and N2 inlet, crude (E)-5,7-dichloro-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (54 g) was dissolved into 360 mL of DME. To this was added a solution of Na2CO3 (23 g, 0.15 mol, in 250 ml, of H2O) followed by the addition of 4-methoxyphenyl boronic acid (22.7 g, 0.15 mol) and Pd(PPh3)4 (1.4 g, 1.2 mmol). The reaction mixture was heated in a 85° C. oil bath for 2 h and then cooled (RT). To this was added 200 mL of EtOAc and the mixture stirred for 5 min. Organic layer was separated and washed with 200 mL H2O and then brine. Organic layer was concentrated to dryness to give 68 g of crude product. This was subjected to column chromatography using 550 g of silica gel and 25/75 to 60/40 EtOAc/heptane. Fractions containing pure product were combined to give 21 g of pure product and other fractions containing a small amount of impurity (by TLC) gave another 20 g of product, albeit less pure. However NMR of both lots was identical. Total of 41 g of product was obtained. Yield 72% over two steps. 1H NMR (300 MHz, CDCl3) δ 3.7 (s, 3H), 3.80 (d, 1H), 3.85 (s, 3H), 4.57 (d, 1H), 4.85 (d, 1H), 5.57 (d, 1H), 6.63 (d, 2H), 6.85-6.95 (m, 4H), 7.16 (d, 1H), 7.3-7.44 (m, 4H).

1. temperaturecooled (RT)
2. customOrganic layer was separated
3. washwashed with 200 mL H2O
4. concentrationOrganic layer was concentrated to dryness
5. customto give 68 g of crude product
6. additionFractions containing pure product