Trimethyl orthoformate → N-Methyl-4-(trifluoromethyl)aniline

Temperatur

90 °C

A mixture of 4-trifluoromethylaniline (6.7 g), trimethylorthoformate (6.6 g) and sulfuric acid (0.22 g) was heated at 90° C. and the methanol formed in the reaction was allowed to distill off. Additional trimethylorthoformate (4 mL) was added twice more. After each addition the reaction mixture was distilled. A final aliquot trimethylorthoformate (5 mL) was added and the reaction mixture was heated at 150° C. for four hours. The reaction mixture was cooled and partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The organic layer was removed, dried over sodium sulfate, and concentrated to a yellow oil. This oil was then suspended in 2N aqueous HCl (100 mL) and then heated at 80° C. for eight hours. The reaction mixture was then cooled, made basic to pH 11 with aqueous NaOH, and extracted with ether. The organic layer was dried over magnesium sulfate and concentrated to an oil. This oil was further purified by chromatography on silica gel (350 g, elute with hexane:ether (60/40)) to give 5.8 g of N-methyl-4-trifluoromethylaniline as a low-melting solid. Condensation of N-methyl-4-trifluoromethylaniline with cyanoacetic acid, as described in Preparation 1 yielded 6.0 g of α-cyano-N-methyl-4-trifluoromethylacetanilide; m.p. 68°-70° C.

1. distillationto distill off
2. additionAdditional trimethylorthoformate (4 mL) was added twice more
3. additionAfter each addition the reaction mixture
4. distillationwas distilled
5. additionA final aliquot trimethylorthoformate (5 mL) was added
6. temperaturethe reaction mixture was heated at 150° C. for four hours
7. temperatureThe reaction mixture was cooled
8. custompartitioned between saturated aqueous sodium bicarbonate and ethyl acetate
9. customThe organic layer was removed
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated to a yellow oil
12. temperatureheated at 80° C. for eight hours
13. temperatureThe reaction mixture was then cooled
14. extractionextracted with ether
15. dry with materialThe organic layer was dried over magnesium sulfate
16. concentrationconcentrated to an oil
17. customThis oil was further purified by chromatography on silica gel (350 g, elute with hexane:ether (60/40))

ORD-Eintrag

ord-475505a2a22248ecbcf231678bce047c

Quelldatensatz

uspto-grants-1991_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05034410