反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 50 °C
PROCEDURE
实验过程
A solution of 1-{[1-(5-Allyloxy-2-tert-butoxycarbonylamino-pentanoyl)-4-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester (the product of step 26F, 2.0 g, 2.94 mmol) in 800 ml of benzene was treated with Grubb's second generation catalyst (375 mg, 0.44 mmol). The reaction mixture was heated to 50° C., stirred under N2 for 2 h, and then concentrated in vacuo. Flash chromatography (silica gel, 25–100% ethyl acetate/hexane) and treatment with activated carbon gave 677.6 mg (˜35%) of 14-tert-butoxycarbonylamino-18-(6-methoxy-isoquinolin-1-yloxy)-2,15-dioxo-10-oxa-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid ethyl ester as a brown collapsed foam: 1H NMR (500 MHz, METHANOL-D4) δ 1.06–1.30 (m, 12H), 1.51–2.03 (m, 6H), 2.41–2.70 (m, 3H), 3.39–3.50 (m, 1H), 3.51–3.61 (m, 1H), 3.77–3.87 (m, 1H), 3.92 (s, 3H), 4.02–4.18 (m, 3H), 4.24 (d, J=6.41 Hz, 1H), 4.36–4.48 (m, 1H), 4.55 (d, J=11.29 Hz, 1H), 4.65 (t, J=8.39 Hz, 1H), 5.55–5.72 (m, 2H), 5.85 (s, 1H), 7.08 (d, J=8.85 Hz, 1H), 7.17 (s, 1H), 7.24 (d, J=5.80 Hz, 1H), 7.89 (d, J=5.80 Hz, 1H), 8.16 (d, J=9.16 Hz, 1H). LC-MS (Method B, retention time: 1.58 min), MS m/z 653 (M++1).
WORKUP
后处理
- concentrationconcentrated in vacuo