Reaktion #40673

Reaktionsgleichung

KOH

19b

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

triethylamine

pivaloyl chloride

HCl

→

19c

Ausbeute 79.7%

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

Ausbeute 79.7%

Lösungsmittel

water

water

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenconcentrated
2. 2
   SonstigeThe crude reaction mixture
3. 3
   Sonstigewas evaporated from toluene
4. 4
   Sonstigeto remove water
5. 5
   workup.STIRRINGThis was stirred at rt for 4 h
6. 6
   Sonstigeto quench
7. 7
   Sonstigethe reaction
8. 8
   ExtraktionThe aqueous layer was extracted with dichloromethane (3×)
9. 9
   Trocknenthe combined organics were dried (MgSO4)
10. 10
    Filtrationfiltered
11. 11
    Sonstigeevaporated
12. 12
    Sonstigeto give the crude product
13. 13
    SonstigeThe crude product was purified by flash chromatography on Biotage

Vorschrift

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).

Quelle