Hydrochloric Acid → 2,2,2-Trifluoro-N-phenylacetamide

Temperatur

-78 °C

A solution of o-bromotrifluoroacetanilide (325 mg, 1.2 mM) in tetrahydrofuran (THF)(20 cm3) was cooled to -78° C. and to this was added methyl lithium (1 molar equivalent of a 1.4 M solution in diethyl ether). This addition was followed 10 minutes later by the introduction of tert-butyllithium (2 molar equivalent of a 1.7 M solution in pentane). The reaction mixture was stirred for 1 hour at -78° C., and then a solution of the chloroindanone (272 mg. 1.2 mM) in THF (3 cm3) added dropwise via a cannula. The solution was allowed to warm slowly to room temperature, and stirred for one hour, then a 10% solution potassium hydroxide in methanol (3 cm3) was introduced. After stirring for 30 minutes, the reaction mixture was poured into 2 M HCl, and extracted with dichloromethane (3 ×10 cm3). The combined organic extracts were dried (Na2SO4 ) and evaporated in vacuo to afford a solid residue which was chromatographed on silica, eluting with 10% ethyl acetate/petroleum ether (60°-80° C.) to yield trifluoroacetanilide (RF 0.4)(50 mg), and the 2-chloro-1-hydroxy-5-methoxy-4,6-dimethyl-1-(2'-trifluoroacetamidophenyl)indane (RF 0.3) (220 mg, 44%). The latter compound is a colourless solid. M.p. 182° C. 1H NMR (CDCl3)δ: 10.7 (1H, br), 8.25 (1H, dd), 7.36 (1H, ddd), 7.06 (1H, s), 6.98 (1H, ddd), 6.39 (1H, dd), 4.76 (1H, dd, J=4.8, 2.7Hz), 3.78 (3H, s), 3.63 (1H, s, exchanges with D2O), 3.11 (2H, 2 ×2nd order multiplets), 2.33 (3H, s), 2.23 (3H, s).

1. additionThis addition
2. temperatureto warm slowly to room temperature
3. stirringstirred for one hour
4. stirringAfter stirring for 30 minutes
5. extractionextracted with dichloromethane (3 ×10 cm3)
6. dry with materialThe combined organic extracts were dried (Na2SO4 )
7. customevaporated in vacuo
8. customto afford a solid residue which
9. customwas chromatographed on silica
10. washeluting with 10% ethyl acetate/petroleum ether (60°-80° C.)

ORD-Eintrag

ord-1e9894d32c674c8e8d6f6189511c54a3

Quelldatensatz

uspto-grants-1993_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05185360