Cesium carbonate → (1-(2-bromoethyl)-3-nitro-1H-pyrazol-5-yl)methanol

Temperature

104 °C

A 1-L three-necked round-bottomed flask equipped with a mechanical stirrer and thermoregulator was purged with nitrogen and charged with (3-nitro-1H-pyrazol-5-yl)methanol 101a (25.0 g, 175 mmol), DMF (250 mL), and cesium carbonate (70.0 g, 215 mmol) was heated at 104° C. for 5 min. The reaction mixture was then cooled to 0° C. using an ice/acetone bath and dibromoethane (329 g, 1.75 mol) was added portionwise (no exotherm). The reaction was stirred at 0° C. for 1 then at room temperature for 4 h. After this time a solution of KH2PO4 (40 g) in water (400 mL) was added slowly. The reaction mixture stirred at room temperature for 30 min. Ethyl acetate (450 mL) was added and the aqueous layer was separated and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water (200 mL), brine (200 mL), dried over sodium sulfate, and the drying agent was removed by filtration. The filtrate was concentrated under reduced pressure to afford an 86% yield (37.5 g) of crude 101b as an orange oil: 1H NMR (300 MHz, CDCl3) δ 6.85 (s, 1H), 4.82 (d, 2H, J=5.4 Hz), 4.66 (t, 2H, J=6.3 Hz), 3.83 (t, 2H, J=6.3 Hz); MS (ESI+) m/z 249.9 (M+H).

1. customA 1-L three-necked round-bottomed flask equipped with a mechanical stirrer
2. customthermoregulator was purged with nitrogen
3. temperatureThe reaction mixture was then cooled to 0° C.
4. stirringThe reaction mixture stirred at room temperature for 30 min
5. customthe aqueous layer was separated
6. extractionextracted with ethyl acetate (2×100 mL)
7. washThe combined organic layers were washed with water (200 mL), brine (200 mL)
8. dry with materialdried over sodium sulfate
9. customthe drying agent was removed by filtration
10. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-5814c694c39a491f9e25e44b738d65d0

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618107B2