Reaktion #748627

Reaktionsgleichung

Ethyl acetate

compound

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

Phosphorus pentoxide

sodium hydroxide

→

titled compound

Ausbeute 44.0%

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

Ausbeute 44.0%

Lösungsmittel

methanesulfonic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe reaction mixture was cooled
2. 2
   Sonstigeat below 40° C.
3. 3
   workup.STIRRINGthe mixture was stirred
4. 4
   Filtrationfiltered
5. 5
   Waschenwashed with ethyl acetate (6.0 liter)
6. 6
   SonstigeThe filtrate was separated
7. 7
   Waschenthe organic layer was washed with 25% ammonia water (1.8 liter) and water (1.8 liter)
8. 8
   WaschenThe organic layer was further washed with water (3.6 liter)
9. 9
   Einengenconcentrated in vacuo at 45-55° C. of the bath temperature
10. 10
    workup.DISSOLUTIONThe residue was dissolved in ethyl acetate (1.2 liter)
11. 11
    workup.ADDITIONn-hexane (4.8 liter) at 50-70° C. and n-hexane (4.8 liter) was added dropwise at the same temperature
12. 12
    TemperaturAfter cooled to below 10° C.
13. 13
    Filtrationthe mixture was filtered
14. 14
    Waschenthe crystalline was washed with chilled ethyl acetate/n-hexane=1/20 (1.2 liter)
15. 15
    SonstigeThe wet product was air-dried
16. 16
    Sonstigedried under reduced pressure at 45-55° C.

Vorschrift

Phosphorus pentoxide (600 g) was dissolved in methanesulfonic acid (6.0 liter) at below 40° C., the solution was added to the compound (1200 g) obtained in Example 1 (1) above and the mixture was stirred under nitrogen atmosphere at 65-75° C. for 3-4 hours. When the reaction was completed, the reaction mixture was cooled, 12N sodium hydroxide aqueous solution was added dropwise thereto at below 40° C. and the mixture was adjusted to pH 10-12. Ethyl acetate (6.0 liter) was added and the mixture was stirred, filtered and washed with ethyl acetate (6.0 liter). The filtrate was separated and the organic layer was washed with 25% ammonia water (1.8 liter) and water (1.8 liter). The organic layer was further washed with water (3.6 liter) and concentrated in vacuo at 45-55° C. of the bath temperature. The residue was dissolved in ethyl acetate (1.2 liter) and n-hexane (4.8 liter) at 50-70° C. and n-hexane (4.8 liter) was added dropwise at the same temperature. After cooled to below 10° C., the mixture was filtered and the crystalline was washed with chilled ethyl acetate/n-hexane=1/20 (1.2 liter). The wet product was air-dried or dried under reduced pressure at 45-55° C. and the titled compound was obtained (496 g, yield 44%).

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