Table 2.
Evaluation of Catalyst Composition and Reaction Solventa
entry | Zr(Ot-Bu)4: HOAt | solvent | conditions | conversionb (%) |
---|---|---|---|---|
1 | 2:1 | toluene | 60 °C, 1 h | 85 |
2 | 1:1 | toluene | 60 °C, 1 h | 96 |
3 | 1:2 | toluene | 60 °C, 1 h | 90 |
4 | 1:3 | toluene | 60 °C, 1 h | 85 |
5 | 1:4 | toluene | 60 °C, 1 h | 78 |
6 | 1:1 | toluene | rt, 12 h | 97c (92d) |
7 | 1:1 | benzene | rt, 12 h | 97c |
8 | 1:1 | DCE | rt, 12 h | 85c |
9 | 1:1 | THF | rt, 12 h | 95c |
10 | 1:1 | 1,4-dioxane | rt, 12 h | 80c |
11 | 1:1 | CH3CN | rt, 12 h | 85c |
Reaction conditions: ethyl hippurate (0.50 mmol), benzylamine (0.50 mmol), Zr(Ot-Bu)4 (0.05 mmol), HOAt and solvent (1 mL).
Conversion based on 1H NMR analysis of the crude reaction mixture.
1.1 equiv of benzylamine employed.
Isolated yield after purification by silica gel chromatography.