Reacción #40673

Ecuación de reacción

KOH

19b

1-(2,2,2-trifluoroacetyl)-1′H-spiro [piperidine4,4′-quinolin]-2′(3′H)-one

triethylamine

pivaloyl chloride

HCl

→

19c

Rendimiento 79.7%

1-pivaloyl-1′H-spiro [piperidine4,4′-quinolin]-2′(3′H)-one

Rendimiento 79.7%

Disolventes

water

water

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Concentraciónconcentrated
2. 2
   OtroThe crude reaction mixture
3. 3
   Otrowas evaporated from toluene
4. 4
   Otroto remove water
5. 5
   workup.STIRRINGThis was stirred at rt for 4 h
6. 6
   Otroto quench
7. 7
   Otrothe reaction
8. 8
   ExtracciónThe aqueous layer was extracted with dichloromethane (3×)
9. 9
   Secadothe combined organics were dried (MgSO4)
10. 10
    Filtraciónfiltered
11. 11
    Otroevaporated
12. 12
    Otroto give the crude product
13. 13
    OtroThe crude product was purified by flash chromatography on Biotage

Procedimiento

KOH (0.65 g, 11.5 mmol) in water (3.0 mL) was added to 19b (1.20 g, 3.8 mmol) in methanol (15 mL) and stirred at rt overnight. The reaction was neutralized with conc. HCl (1 mL) and then concentrated. The crude reaction mixture was evaporated from toluene to remove water. The crude amine was taken up in dichloromethane (30 mL) and triethylamine (2.5 mL, 19.2 mmol) and pivaloyl chloride (0.9 mL, 7.7 mmol) were added. This was stirred at rt for 4 h and then water was added to quench the reaction. The aqueous layer was extracted with dichloromethane (3×) and the combined organics were dried (MgSO4), filtered and evaporated to give the crude product. The crude product was purified by flash chromatography on Biotage using EtOAc/Hexanes (50-100%) to give 19c as a white solid (0.91 g, 79%). (M+H)+=301. 1H NMR (400 MHz, CDCl3) δ ppm 7.90 (s, 1H); 7.30 (d, J=7.3 Hz, 1H); 7.22 (t, J=7.7 Hz, 1H); 7.08 (t, J=7.6 Hz, 1H); 6.78 (d, J=7.8 Hz, 1H); 4.30 (m, 2H); 3.18 (m, 2H); 2.75 (s, 2H); 1.91 (m, 2H); 1.71 (m, 2H); 1.28 (s, 9H).

Fuente