Sodium hydride → 1-Piperazinecarboxylic acid, 4-(3-hydroxy-2-nitrophenyl)-, 1,1-dimethylethyl ester

To a cooled stirring solution of 4-(3-fluoro-2-nitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (1.50 g, 4.61 mmol), and 2-(methylsulfonyl)ethanol (876 mg, 6.92 mmol) in anhydrous DMF (15 mL), under nitrogen, was added, portionwise, sodium hydride (553 mg, 13.8 mmol, 60% oil dispersion). The solution foamed upon the sodium hydride addition. The resulting dark orange solution was stirred, at 0° C., for 30 minutes upon completion of sodium hydride addition. The reaction solution became viscous and additional DMF (5 mL) was added, via syringe, the ice bath removed and the dark solution stirred at room temperature, under nitrogen, for 2 h. The reaction was cooled in an ice bath, quenched with 0.1N hydrochloric acid solution, and transferred to a separatory funnel with ethyl acetate (100 mL). This organic phase was washed with brine (75 mL×3). The aqueous washings were combined and extracted with ethyl acetate (75 mL×3). The organic extracts were combined and washed with saturated aqueous sodium bicarbonate solution (100 mL), brine (100 mL), dried with anhydrous sodium sulfate, filtered and the solvent removed to give an amber colored oil (2.21 g). This oil was adsorbed onto silica and purified by column chromatography, eluting with 50% ethyl acetate in hexane to afford the product as a light yellow colored solid (1.37 g, 92%). Mass Spectrum (+ESI): 324 [M+H]+, 322 [M−H]−.

1. additionunder nitrogen, was added
2. customthe ice bath removed
3. temperatureThe reaction was cooled in an ice bath
4. customquenched with 0.1N hydrochloric acid solution
5. customtransferred to a separatory funnel with ethyl acetate (100 mL)
6. washThis organic phase was washed with brine (75 mL×3)
7. extractionextracted with ethyl acetate (75 mL×3)
8. washwashed with saturated aqueous sodium bicarbonate solution (100 mL), brine (100 mL)
9. dry with materialdried with anhydrous sodium sulfate
10. filtrationfiltered
11. customthe solvent removed

ORD 기록

ord-0521a74df5d14ae7a35cb3420f611ba3

출처 데이터셋

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07531542B2