Sodium hydride → Tert-butyl 4-(4-bromo-3-methyl-pyrazol-1-yl)piperidine-1-carboxylate

참여 물질

반응 조건

반응 단계

Sodium hydride (60% dispersion in mineral oil, 11.53 g) was added portionwise to a stirred solution of 4-bromo-3-methyl-1H-pyrazole (42.2 g) dissolved in DMF (600 ml) over a period of 15 minutes at 0° C. under nitrogen. The resulting slurry was stirred at 0° C. for 1 hour. Then tert-butyl 4-methylsulphonyloxypiperidine-1-carboxylate (73.2 g) was added and the mixture was stirred 1 hour at room temperature then heated to 90° C. overnight. The reaction mixture was then allowed to stir at room temperature over a period of 2 days, quenched with water (2 ml), concentrated to dryness, diluted with ethyl acetate (1500 ml), washed with water (2×1000 ml), brine (1000 ml), dried over magnesium sulfate and concentrated to afford the crude product. A purification by flash chromatography on silica gel eluting with 20% ethyl acetate in petroleum ether afforded tert-butyl 4-(4-bromo-5-methyl-pyrazol-1-yl)piperidine-1-carboxylate (22.5 g) (NMR Spectrum: (DMSOd6) 1.42 (s, 9H), 1.72-1.86 (m, 4H), 2.28 (s, 3H), 2.91 (bs, 2H), 3.96-4.13 (m, 2H), 4.34-4.43 (m, 1H), 7.50 (s, 1H); Mass spectrum: M−tBu: 288,290), and tert-butyl 4-(4-bromo-3-methyl-pyrazol-1-yl)piperidine-1-carboxylate (28.7 g) (NMR Spectrum (DMSOd6): 1.44 (s, 9H), 1.70 (dd, 1H), 1.75 (dd, 1H), 1.91-1.99 (m, 2H), 2.11 (s, 3H), 2.87 (bs, 2H), 4.95-4.10 (m, 2H), 4.21-4.30 (m, 1H), 7.95 (s, 1H); Mass spectrum: M−tBu: 288,290).

출처 및 근거