Acetonitrile → 4,4,4-Trifluoro-3-oxobutanenitrile

Temperature

0 °C

A solution of n-butyllithium in n-hexane (280 ml, 0.44 mole) was added to dry diisopropylamine (64 ml, 0.46 mole) dissolved in dry tetrahydrofuran (400 ml), while maintaining the mixture below 0° C. After stirring at 0° C. for 30 minutes, the mixture was cooled below -72° C. A solution of methyl trifluoroacetate (25.61 g, 0.200 mole), acetonitrile (16.42 g, 0.40 mole) in dry tetrahydrofuran (200 ml) were added dropwise, while maintaining the mixture below -72° C. and after maintaining the mixture at the same temperature for additional 45 minutes, it was warmed to room temperature over 1 hour. Ice-water (700 ml) was added to the mixture and tetrahydrofuran and n-hexane were then evaporated under reduced pressure at a bath temperature of 40° C. The residue was extracted with diethyl ether to remove neutral and basic components, adjusted to pH 1 with 36% HCl and then extracted with methylene chloride to remove by-products such as acetoacetonitrile, etc. The solution was extracted with diethyl ether. After the extract was dried with anhydrous sodium sulfate, p-toluenesulfonic acid (40 mg, 0.0002 mole) was added to the extract. The extract was distilled under the atmospheric pressure and then distilled under reduced pressure to give 26.82 g (crude yield 97.8%) of a cured product. This product was further distilled under reduced pressure to give 16.78 g (61.2%) of the title compound, b.p. 37° C./2.4 mmHg-43° C./2.5 mmHg. When the resulting compound was dissolved in d6 -acetone and its NMR was measured, the ratio of the keto form/the enol form was found to be 17/83.

1. temperaturewhile maintaining the mixture below 0° C
2. temperaturethe mixture was cooled below -72° C
3. temperaturewhile maintaining the mixture below -72° C.
4. temperatureafter maintaining the mixture at the same temperature for additional 45 minutes
5. temperatureit was warmed to room temperature over 1 hour
6. customwere then evaporated under reduced pressure at a bath temperature of 40° C
7. extractionThe residue was extracted with diethyl ether
8. customto remove neutral
9. extractionbasic components, adjusted to pH 1 with 36% HCl and then extracted with methylene chloride
10. customto remove by-products such as acetoacetonitrile, etc. The solution
11. extractionwas extracted with diethyl ether
12. additionwas added to the extract
13. distillationThe extract was distilled under the atmospheric pressure
14. distillationdistilled under reduced pressure
15. customto give 26.82 g (crude yield 97.8%) of a cured product
16. distillationThis product was further distilled under reduced pressure

ORD record

ord-b1666d14047f4ee59ba5ccb12eca75d3

Source dataset

uspto-grants-1990_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04910326