Triphenylphosphine → 3-nitro-1-[1-(tetrahydro-pyran-2-yloxy)-cyclopropylmethyl]-1H-pyrazole

Participants

Reaction Conditions

Reaction Steps

[1-(Tetrahydro-pyran-2-yloxy)-cyclopropyl]-methanol (1.00 g, 5.81 mmol), 3-nitro-1H-pyrazole (prepared in example 3, 656 mg, 5.81 mmol), and triphenylphosphine (1.52 g, 5.81 mmol) were combined and dissolved in anhydrous tetrahydrofuran (30 mL). The reaction was chilled to 0° C. under nitrogen. While stirring, diisopropyl azodicarboxylate (1.72 mL, 8.72 mmol) was added dropwise over a period of 2 min. The ice bath was removed and the reaction continued to stir at 25° C. for 30 min. The reaction was concentrated in vacuo to give a thick golden oil. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 5% ethyl acetate/hexanes to 35% ethyl acetate/hexanes) afforded 3-nitro-1-[1-(tetrahydro-pyran-2-yloxy)-cyclopropylmethyl]-1H-pyrazole (326 mg, 21%) as a white powder: H1-NMR (400 MHz, CDCl3) δ 0.74-0.82 (1H, m), 0.86-0.94 (1H, m), 0.95-1.02 (1H, m), 1.05-1.03 (1H, m), 1.40-1.70 (5H, m), 1.74-1.84 (1H, m), 3.46-3.54 (1H, m), 3.83-3.90 (1H, m), 3.94 (1H, d, J=14.4 Hz), 4.66-4.72 (1H, m), 4.87-4.94 (1H, m), 6.88 (1H, d, J=2.8 Hz), 7.84 (1H, d, J=2.4 Hz).

Provenance & Evidence