Sodium Hydroxide → Tert-butyl 4-[4-(4-amino-1,2,5-oxadiazol-3-yl)phenyl]piperazine-1-carboxylate

To tert-butyl 4-{4-[(Z)-cyano(hydroxyimino)methyl]phenyl}piperazine-1-carboxylate (1.39 g, 4.21 mmol) in EtOH (50 mL) was added an aqueous solution of pre-mixed hydroxylamine hydrochloride (440 mg, 6.32 mmol) and NaHCO3 (535 mg, 6.32 mmol) in water (15 mL) and the reaction was refluxed overnight. An additional aliquot of hydroxylamine hydrochloride (440 mg, 6.32 mmol) and NaHCO3 (535 mg, 6.32 mmol) in water (10 mL) was added and the reaction was refluxed for 2 hours. Aqueous NaOH (1.0 M, 42.1 mL) was added and the reaction was refluxed for 1 hour. An additional aliquot of NaOH (1.0 M, 21 mL) was added and the reaction was refluxed for 3 hours. After cooling to rt, the reaction mixture was poured into brine and the product extracted with EtOAc (2×), dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography over silica gel (EtOAc/Hex, 4/6) to afford tert-butyl 4-[4-(4-amino-1,2,5-oxadiazol-3-yl)phenyl]piperazine-1-carboxylate.

1. temperaturethe reaction was refluxed overnight
2. temperaturethe reaction was refluxed for 2 hours
3. temperaturethe reaction was refluxed for 1 hour
4. temperaturethe reaction was refluxed for 3 hours
5. extractionthe product extracted with EtOAc (2×)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in vacuo
8. custompurified by flash chromatography over silica gel (EtOAc/Hex, 4/6)

ORD 기록

ord-e7db718def9e4c408bcf41be36ee34f1

출처 데이터셋

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07012075B2