Table 3.
Effect of NaH and THF on N-1 regioselectivity.a
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| entry | base | equiv | solvent |
T (°C) |
time (h) |
conv.b (%) |
ratiob 10:11 |
|
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| 1 | Cs2CO3 | 1.5 | THF | rt | 16 | 9 | 5.8:1 |
| 2 | Cs2CO3 | 1.5 | THF | c | 24 | 100 | 6.8:1 |
| 3 | NaH | 1.1 | DMF | rt | 16 | 100 | 1.9:1 |
| 4 | NaH | 1.1 | DMF | c | 24 | 100 | 1.8:1 |
| 5 | LiH | 1.1 | THF | c | 24 | 18 | 28:1 |
| 6 | KH | 1.1 | THF | c | 24 | 100 | 11:1 |
| 7 | NaHMDS | 1.1 | THF | c | 24 | 91 | >99:1 |
| 8 | NaNH2 | 1.1 | THF | c | 24 | 69 | 62:1 |
| 9 | LDA | 1.1 | THF | c | 24 | 26 | >99:1 |
aReaction scale = 1 mmol (9); bdetermined using 1H NMR (see Supporting Information File 1); c0 °C → 50 °C; conv. = conversion of 9 to 10 and 11 only; rt ≈ 20 °C.