p-Toluenesulfonic acid → 5-Nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Participants

Reaction Steps

A suspension of 5-nitro-1H-indazole (24.4 g, 150 mmol) and p-TSA (2.58 g, 14.98 mmol) in DCM (1000 mL) was treated with 3,4-dihydro-2H-pyran (41.0 mL, 449 mmol) over 5 min to provide a solution that was stirred at RT for 6 hr. The resulting dark reaction mixture was added to 2 M NaOH (250 mL) and the organic layer was separated, dried and then concentrated in vacuo to afford a black oil. This material was purified by filtering through a plug of silica (˜700 g), loading and eluting with DCM (>12 L) to yield 5-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole as a pale yellow solid (34.02 g, 133 mmol, 89% yield); Rt 2.06 min, no ionisation observed; 1H NMR (400 MHz, CDCl3) δ: 1.70-1.78 (3H, over-lapping m), 2.14 (2H, m), 2.51 (1H, m), 3.76 (1H, ddd), 4.01 (1H, m), 5.77 (1H, dd), 7.69 (1H, d), 8.21 (1H, d), 8.27 (1H, dd), 8.71 (1H, dd).

Provenance & Evidence