Hydrazine hydrate (1:1) → 6-chloro-5-fluoro-1H-indazole

Temperatur

140 °C

A mixture of 4-chloro-2,5-difluorobenzaldehyde (20.6 g, 105.0 mmol) and hydrazine hydrate (77.2 mL, 1575.2 mmol, 15 eq) in n-butanol (35 mL) was stirred at 140° C. for 3 days. The mixture was cooled to room temperature and poured into ice water (750 mL). The mixture was stirred vigorously for 2 h, and the orange solid was filtered. The filtrate was extracted with EtOAc (3×250 mL), and the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was combined with the orange solid and then purified by MPLC (Biotage®, gradient elution 25% EtOAc/hexane) to give 2.81 g (16%) of a white solid. 1H-NMR (300 MHz, DMSO-d6) 13.3 (broad s, 1H), 8.09 (s, 1H), 7.80 to 7.76 (m, 2H); ES-MS m/z 171.2/173.2 [M+H]+, RT (min) 3.02.

1. temperatureThe mixture was cooled to room temperature
2. stirringThe mixture was stirred vigorously for 2 h
3. filtrationthe orange solid was filtered
4. extractionThe filtrate was extracted with EtOAc (3×250 mL)
5. washthe combined organic phases were washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. custompurified by MPLC (Biotage®, gradient elution 25% EtOAc/hexane)

ORD-Eintrag

ord-ca8e8fec3bcc494cb61974422831e457

Quelldatensatz

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08431695B2