Table 1. Optimization of reaction conditions for the benzylic amination of 4-ethylanisole.
.
| |||||
| entry | solvent | T (°C) | variation | yielda (%) | erb |
|---|---|---|---|---|---|
| 1 | C6H6 | rt | - | 43% | 49:51 |
| 2 | PhCF3 | rt | - | 22% | 48:52 |
| 3 | MeCN | rt | - | 9% | 55:45 |
| 4 | TFE | rt | - | 29% | 53:47 |
| 5 | EtOAc | rt | - | 12% | 60:40 |
| 6 | i-PrOAc | rt | - | 41% | 66:34 |
| 7 | t-BuOAc | rt | - | 13% | 61:39 |
| 8 | i-PrOAc | 4 | - | 56% | 71:29 |
| 9 | i-PrOAc | −10 | - | 14% | 65:35 |
| 10 | i-PrOAc | rt | no base | 34% | 65:35 |
| 11 | i-PrOAc | rt | 0.5 mol % [Rh] | 32% | 64:36 |
Determined by 1H NMR in CDCl3 using trimethyl 1,3,5-benzenetricarboxylate as internal standard.
Determined by chiral HPLC.