Sodium hydride → 1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazole-3-carbaldehyde

To a stirred suspension of NaH (274 mg, 11.4 mmol) in DMF (20 mL) was added solution of 1H-pyrazole-3-carbaldehyde (1.0 g, 10.4 mmol) in DMF (10 mL) dropwise at 0° C. and the mixture was stirred at room temperature for 10 min. The reaction mixture was cooled to 0° C. and SEM-Cl (1.90 g, 11.4 mmol) was added dropwise. The mixture was warmed to room temperature and stirred at the same temperature for 16 h. The reaction mixture was quenched with water and extracted with EtOAc (3×20 mL). The combined organic layers were washed water (20 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 10% EtOAc/hexane as eluent) to provide compound A75-1 (350 mg, 29%) as colorless gum.

1. temperatureThe reaction mixture was cooled to 0° C.
2. temperatureThe mixture was warmed to room temperature
3. stirringstirred at the same temperature for 16 h
4. customThe reaction mixture was quenched with water
5. extractionextracted with EtOAc (3×20 mL)
6. washThe combined organic layers were washed water (20 mL)
7. dry with materialdried over anhydrous Na2SO4
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by column chromatography (silica gel, 10% EtOAc/hexane as eluent)
10. customto provide compound A75-1 (350 mg, 29%) as colorless gum

ORD record

ord-ad9ec22200ef4423ad9fd2fd695dbd77

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365522B2