反应 #70602

反应方程式

Compound 7

4-(8-benzyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione

1-bromoethylbenzene

K2CO3

→

title Compound 32

收率 38.5%

2-(3,4-dimethoxy-benzyl)-4-[8-(1-phenyl-ethyl)-3,8-diaza-bicyclo[3.2.1]oct-3-yl]-isoindole-1,3-dione

收率 38.5%

溶剂

EtOAc

反应条件

后处理

1. 1
   其他for 5 h
2. 2
   过滤The mixture was filtered through Celite®
3. 3
   浓缩concentrated in vacuo
4. 4
   workup.DISSOLUTIONThe crude oil was dissolved in THF (0.4 mL)
5. 5
   温度The mixture was cooled to room temperature
6. 6
   过滤filtered through Celite®
7. 7
   浓缩concentrated in vacuo
8. 8
   其他The crude oil was purified on a Gilson HPLC with a reversed phase Kromasil column (10μ, 100 Å C18, column length 250×50 mm, gradient 90:10-0:100 H2O:MeCN)

实验过程

Compound 7 (50 mg, 0.10 mmol) was hydrogenated (50 psi H2) with 10% Pd/C (5 mg) in EtOAc (1.0 mL) for 5 h. The mixture was filtered through Celite®, and concentrated in vacuo. The crude oil was dissolved in THF (0.4 mL). A portion of 1-bromoethylbenzene (0.03 mL, 0.22 mmol) and K2CO3 (36 mg, 0.26 mmol) were added. The mixture was heated to 50° C. for 4 h. The mixture was cooled to room temperature, filtered through Celite®, and concentrated in vacuo. The crude oil was purified on a Gilson HPLC with a reversed phase Kromasil column (10μ, 100 Å C18, column length 250×50 mm, gradient 90:10-0:100 H2O:MeCN) to give the 19.7 mg (38%) of the title Compound 32 as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.71 (ovdd, J=7.6 Hz, 1 H), 7.49-7.60 (m, 6 H), 7.30 (d, J=8.2 Hz, 1 H), 6.94-7.00 (m, 1 H), 6.86-6.91 (m, 2 H), 4.73 (s, 2 H), 4.00-4.11 (m, 1 H), 3.81 (s, 3 H), 3.80 (s, 3 H), 3.43-3.60 (m, 4 H), 2.67-2.75 (m, 2 H), 2.43-2.51 (m, 2 H), 2.17-2.25 (m, 2 H), and 1.82 (d, J=6.7 Hz, 3 H); MS (ES+) 512.

来源