Reaktion #748629

Reaktionsgleichung

Phosphorus pentoxide

compound

(R)-3-(4-Trifluoromethyl-phenylamino)-valeric acid

water

→

titled compound

Ausbeute 47.0%

(R)-2-Ethyl-6-trifluoromethyl-2,3-dihydro-1H-quinolin-4-one

Ausbeute 47.0%

Lösungsmittel

methanesulfonic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwarmed
2. 2
   Sonstigeat 10-50° C.
3. 3
   Temperaturthe solution was cooled at below 10° C
4. 4
   FiltrationThe precipitated crystalline was collected by filtration
5. 5
   Waschenwashed with water (393 liter)
6. 6
   Waschenthe precipitate was washed again
7. 7
   workup.DISSOLUTIONThe wet crystalline was dissolved in ethyl acetate (26.3 liter)
8. 8
   workup.ADDITIONn-heptane (105 liter) at 60-70° C., and n-heptane (158 liter) was further added at the same temperature
9. 9
   workup.STIRRINGThe solution was stirred at 45-50 for about 3 hours
10. 10
    Temperaturcooled to below 10° C.
11. 11
    Filtrationthe precipitated crystalline was filtered
12. 12
    Waschenwashed with ethyl acetate/n-heptane=1/10 (26.3 liter)
13. 13
    SonstigeThe wet product was dried under reduced pressure at below 50° C.

Vorschrift

Phosphorus pentoxide (13.1 kg) was dissolved in methanesulfonic acid (131 liter) warmed, the solution was added to the compound (26.27 kg) obtained in Example 2 (1) above and the mixture was stirred at 65-75° C. for about 3 hours. To the reaction mixture, was added water (342 liter) dropwise while keeping the temperature at 10-50° C., and then the solution was cooled at below 10° C. The precipitated crystalline was collected by filtration and washed with water (393 liter). When the pH of the washing was acidic, the precipitate was washed again. The wet crystalline was dissolved in ethyl acetate (26.3 liter) and n-heptane (105 liter) at 60-70° C., and n-heptane (158 liter) was further added at the same temperature. The solution was stirred at 45-50 for about 3 hours, cooled to below 10° C., and the precipitated crystalline was filtered and washed with ethyl acetate/n-heptane=1/10 (26.3 liter). The wet product was dried under reduced pressure at below 50° C. to give the titled compound (11.5 kg, yield 47%). MS (APCI) m/z: 244 [M+H]+.

Quelle