Reaktion #805060

Reaktionsgleichung

tert-butyl 2-chloro-6-(trifluoromethyl)isonicotinate

sodium hydride

tert-butyl 4-hydroxypiperidine-1-carboxylate

→

2-{[1-(tert-butoxycarbonyl)piperidin-4-yl]oxy}-6-(trifluoromethyl)isonicotinic acid

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto reach room temperature
2. 2
   workup.STIRRINGthe mixture was stirred at room temperature over five nights
3. 3
   SonstigeThe mixture was quenched by the careful addition of 1N NaOH (15 mL)
4. 4
   workup.STIRRINGto stir overnight
5. 5
   workup.ADDITIONThe reaction was diluted with additional water
6. 6
   Waschenthe aqueous layer was washed with Et2O
7. 7
   workup.ADDITIONThe aqueous layer was then acidified by the addition of c
8. 8
   ExtraktionThe product was extracted with three portions of ethyl acetate
9. 9
   TrocknenThe combined EtOAc extracts were dried over sodium sulfate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated
12. 12
    SonstigeThe product was used without further purification

Vorschrift

To sodium hydride (60% in mineral oil, 0.36 g, 8.9 mmol) in tetrahydrofuran (15 mL) at 0° C. was added tert-butyl 4-hydroxypiperidine-1-carboxylate (1.8 g, 8.9 mmol, Aldrich). The reaction mixture was allowed to reach room temperature and stir for 1 hour. A solution of tert-butyl 2-chloro-6-(trifluoromethyl)isonicotinate (1.0 g, 3.6 mmol, from Step 1) in tetrahydrofuran (4.9 mL, 60. mmol) was introduced and the mixture was stirred at room temperature over five nights. The mixture was quenched by the careful addition of 1N NaOH (15 mL) and allowed to stir overnight. The reaction was diluted with additional water and the aqueous layer was washed with Et2O. The aqueous layer was then acidified by the addition of c.HCl to achieve pH˜3. The product was extracted with three portions of ethyl acetate. The combined EtOAc extracts were dried over sodium sulfate, filtered and concentrated. The product was used without further purification. LCMS (M-tBu+H)+: 335.1.

Quelle