4-Methoxyphenylhydrazine hydrochloride → HCID 66738820, compound

Temperature

0 °C

(Z)—N-(3-(dimethylamino)-2-(trifluoromethyl)allylidene)-N-methyl methanaminium hexafluorophosphate (4.46 g, 13.1 mmol) and 4-methoxyphenyl hydrazine hydrochloride (2.55 g, 14.6 mmol) were suspended in tetrahydrofuran (50 mL) and cooled to 0° C. Sodium methoxide (820 mg, 14 mmol) was added as a solid in one portion. The mixture was stirred at 0° C. for 10 minutes. The ice bath was removed and the mixture was stirred at room temperature for 1 hour. The mixture was cooled again to 0° C. and trifluoroacetic acid (3 mL) was added. The ice bath was removed and the mixture heated to reflux. After 18 hours at reflux, the reaction was cooled to room temperature and diluted with ethyl acetate (50 mL). The mixture was washed successively with saturated sodium bicarbonate until the washings were basic. The combined aqueous washings were extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude material was passed through a plug of silica gel (100 g), eluting with dichloromethane (600 mL). The filtrate was concentrated to give 1-(4-methoxyphenyl)-4-(trifluoromethyl)-1H-pyrazole (2.7 g, 85%). 1H NMR (400 MHz, CDCl3, δ): 8.06 (s, 1H), 7.85 (s, 1H), 7.53-7.59 (m, 2H), 6.94-7.00 (m, 2H), 3.84 (s, 3H).

1. customThe ice bath was removed
2. stirringthe mixture was stirred at room temperature for 1 hour
3. temperatureThe mixture was cooled again to 0° C.
4. additiontrifluoroacetic acid (3 mL) was added
5. customThe ice bath was removed
6. temperaturethe mixture heated to reflux
7. temperatureAfter 18 hours at reflux
8. temperaturethe reaction was cooled to room temperature
9. additiondiluted with ethyl acetate (50 mL)
10. washThe mixture was washed successively with saturated sodium bicarbonate until the washings
11. extractionThe combined aqueous washings were extracted with ethyl acetate
12. washThe combined organic layers were washed with brine
13. dry with materialdried over magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated
16. washeluting with dichloromethane (600 mL)
17. concentrationThe filtrate was concentrated

ORD record

ord-54dd76127fc6444fa5ec2bb812aeca7a

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507533B2