Thionyl Chloride → 5-[3-(1,1-dimethylethyl)-1H-pyrazol-1-yl]-3-[3-(trifluoromethyl)phenyl]-4-thiazolidinone

Temperature

0 °C

To a stirred solution of thionyl chloride (5.3 mL, 73 mmol) in 120 mL of methylene chloride at ˜10° C. was slowly added 3-(1,1-dimethylethyl)-1H-pyrazole (11.32 g, 91 mmol). The resulting solution was stirred for ˜20 minutes and was then cooled further to ˜0° C. To this solution was added N,N-diisopropylethylamine (26.5 mL, 152 mmol) dropwise at ˜0° C. and then 5-hydroxy-3-[3-(trifluoromethyl)phenyl]4thiazolidinone (16 g, 61 mmol) portionwise at temperatures between 0° C. and 10° C. After the addition, the reaction mixture was allowed to warm up to room temperature, and stirred at room temperature for 3 days. To the reaction mixture was then added 120 mL of concentrated sodium bicarbonate aqueous solution. The methylene chloride layer was separated and the aqueous layer was extracted twice with methylene chloride (˜120 mL each). The methylene chloride layers were combined, dried over MgSO4 and then concentrated. The residue was loaded on silica gel in a flash chromatography column and eluted with hexanes followed by methylene chloride to give 15.74 g of a crude product. The crude product was further purified by trituration in hexanes followed by filtration to give the title compound, a compound of this invention, as a tan solid (11.8 g) melting at 66–69° C.

1. customat ˜10° C.
2. customportionwise at temperatures between 0° C. and 10° C
3. additionAfter the addition
4. temperatureto warm up to room temperature
5. stirringstirred at room temperature for 3 days
6. customThe methylene chloride layer was separated
7. extractionthe aqueous layer was extracted twice with methylene chloride (˜120 mL each)
8. dry with materialdried over MgSO4
9. concentrationconcentrated
10. washeluted with hexanes
11. customto give 15.74 g of a crude product
12. customThe crude product was further purified by trituration in hexanes
13. filtrationfollowed by filtration

ORD record

ord-85489a5bac5147dd843e8e521640e14c

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07138361B2