Acetyl chloride → (2S)-3,3-dimethyl-1-[3-(3-pyridinyl)-1H-pyrazol-1-yl]-2-butanol

Participants

Reaction Steps

To a solution of 0.38 g (2.62 mmol) of 3-(1H-pyrazol-3-yl)pyridine and 0.47 g (2.62 mmol) of (4S)-4-tert-butyl-1,3,2-dioxathiolane 2,2-dioxide in 15 mL of acetonitrile was added 1.3 g of a potassium fluoride/alumina mixture [prepared by mixing 10 g of potassium fluoride, 200 mL of water, and 15 g of activated neutral alumina (Brockmann I, 150 mesh) and concentrating at 55° C.]. The mixture was stirred at ambient temperature for 4 h. Then, a solution of 2 mL of acetyl chloride in 10 mL of methanol was added to the reaction mixture. After 18 h, saturated aqueous sodium bicarbonate was added, the mixture was filtered, and the filter cake was rinsed with methanol. The filtrate was concentrated, and the residue was partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The organic phase was dried over sodium sulfate and concentrated to provide 0.6 g (94%) of (2S)-3,3-dimethyl-1-[3-(3-pyridinyl)-1H-pyrazol-1-yl]-2-butanol as a yellow solid. 1H-NMR (DMSO-d6): δ 8.97 (s, 1H), 8.45 (d, J=4 Hz, 1H), 8.1 (t, J=8 Hz, 1H), 7.76 (d, J=2 Hz, 1H), 7.38 (dd, J=8 Hz, J=5 Hz, 1H), 4.86 (d, J=6 Hz, 1H), 4.27 (dd, J=13 Hz, J=2 Hz, 1H), 3.90 (dd, J=14 Hz, J=10 Hz, 1H), 3.5–3.4 (m, 1H), 0.90(s, 9H).

Provenance & Evidence