Water → (4-chlorophenyl)[2-(4H-1,2,4-triazol-3-yl)-3-thienyl]methanone

Temperature

-78 °C

To a solution of 3-(3-bromo-2-thienyl)-4H-1,2,4-triazole (15.05 g, 65.41 mmol) in Tetrahydrofuran (500 mL, 6000 mmol) was added dropwise 2.5M BuLi in hexanes (104 mL, 262 mmol) at −70° C. (internal temperature) and the solution was stirred for 30 min at −78° C. A solution of 4-chloro-N-methoxy-N-methylbenzamide (41.24 g, 206.6 mmol) in tetrahydrofuran (80 mL, 1000 mmol) was then added dropwise into the suspension. The resulting mixture was stirred for 60 min at −78° C. Ammonium chloride (17.49 g, 327.0 mmol) in water (100 mL, 6000 mmol) was added to the mixture at −78° C. and the mixture was stirred for 15 min before being warmed to rt. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, and then filtered to remove drying agent. The solvent was evaporated and the residue was purified by chromatography to afford (4-chlorophenyl)[2-(4H-1,2,4-triazol-3-yl)-3-thienyl]methanone as white solid (16.8 g, 88.5%). LCMS: (FA) ES+ 289.9, 291.8

1. stirringThe resulting mixture was stirred for 60 min at −78° C
2. stirringthe mixture was stirred for 15 min
3. temperaturebefore being warmed to rt
4. customThe organic layer was separated
5. extractionthe aqueous layer was extracted with EtOAc
6. washThe combined organic layers were washed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. customto remove
10. customdrying agent
11. customThe solvent was evaporated
12. customthe residue was purified by chromatography

ORD record

ord-797df526b11f49b3a02cb914be28c65e

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796271B2