Hydrochloric Acid → 3-(3-chloro-1H-pyrazol-1-yl)pyridine

Participants

Reaction Conditions

Reaction Steps

To a 3-neck round bottomed flask (250 mL) was charged 3-(3-amino-1H-pyrazol-1-yl)pyridine (5.00 g, 31.2 mmol) and hydrogen chloride (37 wt %, 15 mL). The mixture was cooled to 0° C. A solution of sodium nitrite (4.31 g, 62.4 mmol) in water (15 mL) was added in portions at <1° C. over 20 minutes and the resulting brown solution was stirred at <0° C. for 2 hours. To a separate 3-neck round bottomed flask (250 mL) was charged copper(II) chloride (5.04 g, 37.5 mmol) and toluene (30 mL). It was cooled to 0° C. and the yellow solution was added in portions at <1° C. over 15 minutes. The resulting mixture was allowed to warm up, off-gassing was observed when the reaction temperature reached 18° C. The reaction was stirred at 20° C. for 18 hours. The reaction was basified with 50 wt % sodium hydroxide to pH ˜10. Celite® (10 g) was added and the resulting suspension was stirred for 10 minutes. The suspension was filtered through a Celite® pad (10 g) and the filter cake was rinsed with ethyl acetate (2×50 mL). The layers of the filtrates were separated and the aqueous layer was extracted with ethyl acetate (100 mL). The organic layers were concentrated to dryness and the residue was purified by flash column chromatography using 0-60% ethyl acetate/hexanes as eluent. The fractions containing the desired product were concentrated to give the title compound as a white solid (3.80 g, 68%): mp 104-106° C.; 1H NMR (400 MHz, CDCl3) δ 8.93 (d, J=2.7 Hz, 1H), 8.57 (dd, J=4.8, 1.4 Hz, 1H), 8.02 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.91 (d, J=2.6 Hz, 1H), 7.47-7.34 (M, 1H), 6.45 (d, J=2.6 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 148.01, 142.72, 140.12, 135.99, 128.64, 126.41, 124.01, 108.08; EIMS m/z 179 ([M]+).

Provenance & Evidence