4-Bromopyrazole → HCID 58293782, compound

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.

1. additionwas added dropwise
2. temperaturebefore refluxing overnight
3. temperatureThe reaction was cooled to room temperature
4. customquenched by addition of aqueous NaCl (300 mL)
5. extractionextracted with ethyl acetate (3×200 mL)
6. washwashed with 1% aqueous LiCl (200 mL×3)
7. customdried
8. concentrationconcentrated in vacuo
9. customThe resulting crude bromide (Compound 1008) was purified by silica gel chromatography (0-25% Ethyl Acetate in Hexanes)

ORD record

ord-418ccf8a08dc42eebcf8177c55ace55e

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481524B2