Table 2.
Azido PEG Reactions with DEBD
| Entry | R | Mol. Wt. | DEBD Eq. | Solvent | Temp. (time) | Yield (%) | N3 Substitution (%) |
|---|---|---|---|---|---|---|---|
| 1 | OMe | 3.5 | 2.0 | CH3CN | reflux (4 h) | 91 | >99 |
| 2 | OMe | 18.6 | 2.0 | CH3CN | reflux (36 h) | 97 | >99 |
| 3 | NHBoc | 2.1 | 2.0 | CH3CN | reflux (16 h) | 93 | >99 |
| 4 | NHBoc | 12.3 | 2.0 | CH3CN | reflux (27 h) | 89 | >99 |
| 5 | NH2 | 2.1 | 2.0 | CH3CN | reflux (15 h) | –a | – |
| 6 | NH2 | 12.5 | 2.0 | CH3CN | reflux (38 h) | –a | – |
| 7 | OH | 5.0 | 2.0 | CH3CN | reflux (8 h) | 89b | >99 |
| 8 | OH | 11.1 | 1.2 | CH3CN | 40 °C (36 h) | –b | – |
| 9 | OH | 11.1 | 2.0 | CH3CN | 75 °C (36 h) | –b | – |
| 10 | OH | 11.1 | 2.0 | THF | 60 °C (16 h) | –b | – |
| 11 | OH | 2.1 | 2.0 | CHCl3 | 40 °C (72 h) | 83 | >99 |
| 12 | OH | 2.1 | 5.0 | CHCl3 | reflux (24 h) | 88 | >99 |
| 13 | OH | 11.1 | 1.2 | CHCl3 | 40 °C (72 h) | 88 | >99 |
| 14 | OH | 11.1 | 3.0 | CHCl3 | 65 °C (48 h) | 85 | >99 |
| 15 | CO2H | 2.1 | 5.0 | CHCl3 | reflux (24 h) | –b | – |
| 16 | CO2H | 2.1 | 5.0 | CHCl3 | r.t. (36 h) | 85 | >99 |
| 17 | CO2H | 11.1 | 5.0 | CHCl3 | r.t. (36 h) | 96 | >99 |
a
Mixture of click and Michael addition products.
b
By‐products detected in NMR.