Lithium Hydroxide → (2R)-4-(4-cyano-1H-pyrazol-1-yl)-2-methyl-2-(methylsulfonyl)butanoic acid

온도

50 °C

To a solution of 4-cyanopyrazole (0.150 g, 1.61 mmol, 1 eq) in acetonitrile (10 mL) was added cesium carbonate (1.31 g, 4.03 mmol, 2.5 eq), sodium iodide (0.048 mg, 0.322 mmol, 0.2 eq) and (R)-ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate (0.555 g, 1.93 mmol, 1.2 eq). The mixture was heated at 50° C. overnight. The reaction mixture was cooled to room temperature and was filtered via Buchner funnel, and eluted with EtOAc. The filtrate was concentrated under reduced pressure and was diluted with up in tetrahydrofuran (5 mL) and water (5 mL). Lithium hydroxide (0.116 g, 4.83 mmol, 3 eq) was added, and the reaction mixture was allowed to stir at room temperature for four hours. The reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate (10 mL), and concentrated again. This yielded (2R)-4-(4-cyano-1H-pyrazol-1-yl)-2-methyl-2-(methylsulfonyl)butanoic acid as a yellow oil, which was carried on crude in the next step. LC-MS M+H+272.2.

1. temperatureThe reaction mixture was cooled to room temperature
2. filtrationwas filtered via Buchner funnel
3. washeluted with EtOAc
4. concentrationThe filtrate was concentrated under reduced pressure
5. additionwas diluted with up in tetrahydrofuran (5 mL) and water (5 mL)
6. concentrationThe reaction mixture was concentrated under reduced pressure
7. additiondiluted with ethyl acetate (10 mL)
8. concentrationconcentrated again

ORD 기록

ord-adc1c3a17ca244c39114b88f21c3cb9a

출처 데이터셋

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08809333B2