Triethylamine → 1-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

To tert-butyl 4-hydroxypiperidine-1-carboxylate (402 mg, 2.0 mmol) in methylene chloride (20 mL) and triethylamine (303 mg, 3.0 mmol) at 4° C. was added methanesulfonyl chloride (274 mg, 2.4 mmol) drop-wise. The reaction was brought to ambient temperature and was stirred for 1 hour. The reaction mixture was concentrated in vacuo and diluted in diethyl ether (20 mL). The solution was washed with 1N hydrochloric acid (3 mL), water (3 mL), and saturated sodium bicarbonate (3 mL). The organics were dried (sodium sulfate) and concentrated in vacuo to afford tert-butyl4-(methylsulfonyloxy)piperidine-1-carboxylate in quantitative yield. The product was used directly in the next step without further purification. A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (427 mg, 2.2 mmol), tert-butyl4-(methylsulfonyloxy)piperidine-1-carboxylate (2.0 mmol), and cesium carbonate (847 mg, 2.6 mmol) in DMF (5 mL) was stirred at 100° C. overnight. The mixture was diluted with saturated aqueous NaHCO3 and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated to provide crude pale yellow oil 884 mg. MS (m/z): 378 (M+H)+.

1. customwas brought to ambient temperature
2. concentrationThe reaction mixture was concentrated in vacuo
3. additiondiluted in diethyl ether (20 mL)
4. washThe solution was washed with 1N hydrochloric acid (3 mL), water (3 mL), and saturated sodium bicarbonate (3 mL)
5. dry with materialThe organics were dried (sodium sulfate)
6. concentrationconcentrated in vacuo

ORD record

ord-1591a681524640e8bc1e380c308e8253

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434726B2