4-Bromopyrazole → HCID 58293782, compound

Participants

Reaction Steps

To a solution of 4-bromopyrazole (4.68 g, 31.83 mmol) in DMF (300 mL) at 0° C. was added sodium hydride (60% on mineral oil, 1.27 g, 31.83 mmol). The solution was allowed to stir at 0° C. for one hour, at which point a solution of (S)-3-Methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (Compound 1007, which was prepared from (S)-tert-butyl 3-hydroxypiperidine-1-carboxylate, 9.78 g, 31.83 mmol) in DMF (50 mL) was added dropwise. The reaction mixture was allowed to stir at room temperature for 1 hour before refluxing overnight. Disappearance of both starting materials was tracked by TLC (1:1 Hexanes/Ethyl Acetate). The reaction was cooled to room temperature and quenched by addition of aqueous NaCl (300 mL), extracted with ethyl acetate (3×200 mL), washed with 1% aqueous LiCl (200 mL×3), dried and concentrated in vacuo. The resulting crude bromide (Compound 1008) was purified by silica gel chromatography (0-25% Ethyl Acetate in Hexanes) to give (R)-tert-butyl 3-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylate as a colourless waxy solid (4.54 g, 43% yield); 1H NMR (300.0 MHz, CDCl3): δ 7.42 (s, 1H), 7.40 (s, 1H), 4.13-4.05 (m, 2H), 3.82 (d, J=13.2 Hz, 1H), 3.20 (dd, J=10.3, 14.0 Hz, 1H), 2.94-2.85 (m, 1H), 2.08-1.97 (m, 2H), 1.74-1.45 (m, 2H) and 1.39 (s, 9H) ppm.

Provenance & Evidence