Table 4. Optimization of Reaction Conditions with Cyclohexylaminea.
| entry | chloride (equiv) | base (equiv) | T (°C) | time (h) | solvent | ratio of 30l:31l (%)b |
|---|---|---|---|---|---|---|
| 1 | 1.2 | Cs2CO3 (3.2) | 160 (MW) | 1/2 | DMF | 57:0 |
| 2 | 1.2 | Cs2CO3 (3.2) | 160 | 8 | DMF | 58:0 |
| 3 | 1.7 | Cs2CO3 (3.2) | 160 (MW) | 1/2 | DMF | 31:0 |
| 4 | 1.2 | Cs2CO3 (3.7) | 160 (MW) | 1/2 | DMF | 48:0 |
| 5 | 1.2 | Cs2CO3 (3.2) | 160 (MW) | 1/2 | N,N-DMA | 25:0 |
| 6 | 1.2 | Cs2CO3 (3.2) | 160 (MW) | 1/2 | N,N-DMA | 47:0 |
| 7 | 1.2 | DBU (3.2) | reflux | 2 | MeCN | 0:95 |
| 8 | 1.2 | NaH (3.2) | 150 | 2 | N,N-DMA | 0:42 |
a
Reaction conditions: Benzoxazole-2-thiol (0.16 mmol, 25 mg), cyclohexylamine (0.16 mmol), base, ClCH2COCl, solvent (1 mL).
b
Conversion estimated from LC–MS traces at 210–500 nm.