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
- 80 °C
PROCEDURE
实验过程
To a solution of N-cyclopentyl-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-[(1S)-1-phenylprop-2-en-1-yl]pent-4-enamide (330 mg) dissolved in Toluene (30 mL) at 80° C. under N2 was added Grubbs catalyst (2nd generation) (33 mg) and the reaction mixture was stirred at 80° C. for 35 minutes, cooled to RT and concentrated in vacuo. The crude product was directly purified via flash chromatography (gradient—10%, 15% EtOAc/hexanes) to give the title compounds, 2-[(3R,7S)-1-cyclopentyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl]-1H-isoindole-1,3(2H)-dione (8d) (182 mg) and 2-[(3S,7S)-1-cyclopentyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl]-1H-isoindole-1,3(2H)-dione (8c) (95 mg, combined yield of 90%). (8d) 1H NMR (300 MHz, CDCl3) δ 1.44-1.70 (m, 6H), 1.85-2.04 (m, 3H), 2.36-2.43 (m, 1H), 3.69-3.81 (m, 1H), 5.02-5.15 (m, 2H), 5.18-5.30 (m, 1H), 5.98-6.05 (m, 1H), 6.35-6.42 (m, 1H), 7.19-7.52 (m, 5H), 7.64-7.87 (m, 4H). MS APCI, m/z=401 (M+1), LC/MS, 2.73 min. (8c) 1H NMR (300 MHz, CDCl3) δ 1.14-1.88 (m, 9H), 2.25-2.32 (m, 1H), 3.37-3.48 (m, 1H), 4.01-4.11 (m, 1H), 5.30 (dd, 1H, J=13 Hz, J=4 Hz), 5.52 (d, 1H, J=7 Hz), 6.04-6.11 (m, 1H), 6.43-6.50 (m, 1H), 7.29-7.55 (m, 5H), 7.69-7.90 (m, 4H). MS APCI, m/z=401 (M+1), LC/MS, 2.80.
WORKUP
后处理
- temperaturecooled to RT
- concentrationconcentrated in vacuo
- customThe crude product was directly purified via flash chromatography (gradient—10%, 15% EtOAc/hexanes)