N,N,N',N'-Tetramethylethylenediamine → HCID 54299138, compound

Temperature

-78 °C

To a solution of 4.50 g (18.0 mmol) of 5-(1-methylethyl)-4-(4-methylthiophenyl)thiazole and 3.15 ml (20.9 mmol) of tetramethylethylenediamine in 85 ml of tetrahydrofuran at -78° C. was added dropwise 20.0 ml (32.0 mmol) of n-butyl lithium (1.6M in hexane). The resulting solution was stirred for 1 hour at -78° C., and then 5.6 ml (50 mmol) of hexafluoroacetone was added dropwise. The mixture was stirred for 1 hour at -78° C. and then quenched by the rapid addition of 50 ml of sodium bicarbonate solution. After warming to 25° C., the organic and aqueous phases were separated and the aqueous phase was extracted with tetrahydrofuran. The combined organic phases were then washed with brine, dried over anhydrous potassium carbonate, filtered, and concentrated. The residue was dissolved in a mixture of 150 ml of ethanol and 30 ml of 4N hydrochloric acid; and the solution was stirred overnight at 25° C. The solution was concentrated in vacuo to remove the ethanol and the resulting aqueous mixture was extracted with diethyl ether. The combined organic phases were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (elution-benzene) to provide 5.9 g of 5-(1-methylethyl)-4-(4-methylthiophenyl)-α,α-bis(trifluoromethyl)thiazole-2-methanol as a light orange oil.

1. stirringThe mixture was stirred for 1 hour at -78° C.
2. customquenched by the rapid addition of 50 ml of sodium bicarbonate solution
3. temperatureAfter warming to 25° C.
4. customthe organic and aqueous phases were separated
5. extractionthe aqueous phase was extracted with tetrahydrofuran
6. washThe combined organic phases were then washed with brine
7. dry with materialdried over anhydrous potassium carbonate
8. filtrationfiltered
9. concentrationconcentrated
10. dissolutionThe residue was dissolved in a mixture of 150 ml of ethanol and 30 ml of 4N hydrochloric acid
11. stirringand the solution was stirred overnight at 25° C
12. concentrationThe solution was concentrated in vacuo
13. customto remove the ethanol
14. extractionthe resulting aqueous mixture was extracted with diethyl ether
15. washThe combined organic phases were washed with brine
16. dry with materialdried over anhydrous magnesium sulfate
17. filtrationfiltered
18. concentrationconcentrated
19. customThe crude product was purified by flash chromatography on silica gel (elution-benzene)

ORD record

ord-383f0db5c7df4e6dbf1b97dc543d8edf

Source dataset

uspto-grants-1986_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04632930