Hydrochloric Acid → 1-[5-(2H-Tetrazol-5-yl)-1,3,4-thiadiazol-2-yl}-4-[2-(trifluoromethyl)phenoxy]piperidine

温度

130 °C

A suspension of 5-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3,4-thiadiazole-2-carbonitrile (4.99 g, 14.1 mmol), NaN3 (4.65 g, 71.5 mmol) and pyridinium hydrochloride (3.43 g, 29.7 mmol) in NMP (50 mL) was heated at 130° C. for 18 h. The reaction mixture was cooled to room temperature and poured into aqueous 0.5 N HCl, extracted with EtOAc, washed three times with aqueous 0.5 N HCl, and with aqueous brine solution. The organic layer was dried (Na2SO4) and filtered. Evaporation of the solvent was followed by trituration in a mixture of MeOH/Et2O/heptane (1:1:6) (v/v) with stirring for 4 h at room temperature. After this time, the suspension was cooled with an ice-water bath and the title compound was collected by filtration as a white solid. The material was dried under high vacuum by heating at 50° C. for 1-2 h.

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionextracted with EtOAc
3. washwashed three times with aqueous 0.5 N HCl
4. dry with materialThe organic layer was dried (Na2SO4)
5. filtrationfiltered
6. customEvaporation of the solvent
7. additionwas followed by trituration in a mixture of MeOH/Et2O/heptane (1:1:6) (v/v)
8. temperatureAfter this time, the suspension was cooled with an ice-water bath
9. filtrationthe title compound was collected by filtration as a white solid
10. customThe material was dried under high vacuum
11. temperatureby heating at 50° C. for 1-2 h.

ORDレコード

ord-45b7f743e6d849329f9e563d55a1e0b9

出典データセット

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08063224B2